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Tumor and endothelial cell invasion of basement membranes

The Matrigel Chemoinvasion Assay As A Tool For Dissecting Molecular Mechanisms

  • Seminar
  • Published:
Pathology & Oncology Research

Abstract

The spread of cancer cells from a primary tumor to distant organs is the major cause of death of cancer patients. Metastatic lesions are often resistent to cancer therapy because of the progressive phenotypic changes that they have undergone. Several genetic and epigenetic factors, both in the cell and in the host, contribute to the development of tumor progression towards metastases. In this review we will analyze the steps involved in tumor metastases, which can be potential targets for anti-metastatic therapy. One of the most critical events in cancer metastasis is the invasion of basement membranes. An assay which we developed over ten years ago, the Matrigel “chemoinvasion” assay, has been a useful tool for studying the mechanisms involved in tumor and endothelial cell invasion of basement membranes and for the screening of anti-invasive agents. Here we will describe the assay and review some of the major results obtained with it.

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References

  1. Ahmad A, Hart IR: Mechanisms of metastasis. Crit Rev Oncol Hematol 26:163–173, 1997.

    Article  PubMed  CAS  Google Scholar 

  2. Ahonen M, Baker AH, Kahari VM: Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells. Cancer Res. 58:2310–2315, 1998.

    PubMed  CAS  Google Scholar 

  3. Akiyama SK, Olden K, Yamada KM: Fibronectin and integrins in invasion and metastasis. Cancer Metastasis Rev 14:173–189, 1995.

    Article  PubMed  CAS  Google Scholar 

  4. Albini A, Barillari G, Benelli R, et al: Angiogenic properties of human immunodeficiency virus type 1 Tat protein. Proc Natl Acad Sci USA 92:4838–4842, 1995.

    Article  PubMed  CAS  Google Scholar 

  5. Albini A, D’Agostini F, Giunciuglio D, et al: Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N-acetylcysteine. Int J Cancer 61:121–129, 1995.

    Article  PubMed  CAS  Google Scholar 

  6. Albini A, Iwamoto Y, Kleinman HK, et al: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 47:3239–3245, 1987.

    PubMed  CAS  Google Scholar 

  7. Albini A, Melchiori A, Santi L, et al: Tumor cell invasion inhibited by TIMP-2. J Natl Cancer Inst 83:775–779, 1991.

    Article  PubMed  CAS  Google Scholar 

  8. Albini A, Muller PK, Parodi S: A method to select cell populations with enhanced chemotactic activity. Bioscience Rep. 4:311–318, 1984.

    Article  CAS  Google Scholar 

  9. Alessandro R, Kohn EC: Molecular genetics of cancer. Tumor invasion and angiogenesis. Cancer 76:1874–1877, 1995.

    Article  PubMed  CAS  Google Scholar 

  10. Alessandro R, Spoonster J, Wersto RP, et al: Signal transduction as a therapeutic target. Curr Top Microbiol Immunol 213:167–188, 1996.

    PubMed  CAS  Google Scholar 

  11. Andreasen PA, Kjoller L, Christensen L, et al: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72:1–22, 1997.

    Article  PubMed  CAS  Google Scholar 

  12. Aota S,Yamada KM: Integrin functions and signal transduction. Adv Exp Med Biol 669–682, 1997.

  13. Arbiser JL, Moses MA, Fernandez CA, et al: Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 94:861–866, 1997.

    Article  PubMed  CAS  Google Scholar 

  14. Baker AH, Zaltsman AB, George SJ, et al: Divergent effects of tissue inhibitor of metalloproteinase-1,-2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. J Clin Invest 101:1478–1487, 1998.

    Article  PubMed  CAS  Google Scholar 

  15. Bardelli A, Comoglio PM: Scatter factor receptors are key players in a unique multistep program leading to invasive growth. Ciba Found Symp 212:133–144, 1997.

    PubMed  CAS  Google Scholar 

  16. Berditchevski F, Tolias KF, Wong K, et al: A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem 272:2595–2598, 1997.

    Article  PubMed  CAS  Google Scholar 

  17. Bian J, Wang Y, Smith RM, et al: Suppression of in vivo tumor growth and induction of suspension cell death by tissue inhibitor of metalloproteinases (TIMP)-3. Carcinogenesis 17:1805–1811, 1996.

    Article  PubMed  CAS  Google Scholar 

  18. Birchmeier W: E-cadherin as a tumor (invasion) suppressor gene. Bioessays 17:97–99, 1995.

    Article  PubMed  CAS  Google Scholar 

  19. Birehmeier W, Brinkmann V, Niemann C, et al: Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells. Ciba Found Symp 212:230–240; discussion 240–246, 1997.

    Google Scholar 

  20. Boyd D:. Invasion and metastasis. Cancer Metast Rev 15: 77–89, 1996.

    Article  CAS  Google Scholar 

  21. Brooks P, Clark A, Cheresh D: Requirement of vascular integrin αvβ3 for angiogenesis. Science 264:569–571, 1994.

    Article  PubMed  CAS  Google Scholar 

  22. Brooks P, Montgomery A, Rosenfeld M, et al: D. Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164, 1994.

    Article  PubMed  CAS  Google Scholar 

  23. Brown MA. Tumor suppressor genes and human cancer. Adv Genet 36:45–135, 1997.

    PubMed  CAS  Google Scholar 

  24. Brown PD. Matrix metalloproteinase inhibitors in the treatment of cancer. Med Oncol 14:1–10, 1997.

    PubMed  CAS  Google Scholar 

  25. Bussolino F,Albini A,Camussi G,et al: Role of soluble mediators in angiogenesis. Eur J Cancer 2401–2412, 1996.

  26. Chambers AF, Matrisian LM: Changing views in the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270, 1997.

    Article  PubMed  CAS  Google Scholar 

  27. Chao C, Lotz MM, Clarke AC, et al: A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells. Cancer Res 56:4811–4819, 1996.

    PubMed  CAS  Google Scholar 

  28. Chen H, Paradies NE, Fedor-Chaiken M, et al: E-cadherin mediates adhesion and suppresses cell motility via distinct mechanisms. J Cell Sci 110:345–356, 1997.

    PubMed  CAS  Google Scholar 

  29. Chintala SK, Fueyo J, Gomez-Manzano C, et al: Adenovirus-mediated pl6/CDKN2 gene transfer suppresses glioma invasion in vitro. Oncogene 15:2049–2057, 1997.

    Article  PubMed  CAS  Google Scholar 

  30. Chintala SK, Sawaya R, Rao, JS. Modulation of matrix metalloprotease-2 and invasion in human glioma cells by alpha3betal integrin. Cancer Lett 103:201–208, 1996.

    Article  PubMed  CAS  Google Scholar 

  31. Chirivi RG, Chiodoni C, Musiani P, et al: IL-1 alpha gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice. Int J Cancer 67:856–863, 1996.

    Article  PubMed  CAS  Google Scholar 

  32. Claffey KP, Robinson GS: Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis. Cancer Metastasis Rev 15:165–176, 1996.

    Article  PubMed  CAS  Google Scholar 

  33. Cockett Ml, Murphy G, Birch ML, et al: Matrix metalloproteinases and metastatic cancer. Biochem Soc Symp 63:295–313, 1998.

    PubMed  CAS  Google Scholar 

  34. Coffey DS: Self-organization, complexity and chaos: the new biology for medicine. Nat Med 4:882–885, 1998.

    Article  PubMed  CAS  Google Scholar 

  35. Calville NP, Willoughby DA: Growth factors in angiogenesis: current interest and therapeutic potential. Mol Med Today 3:14–23, 1997.

    Article  Google Scholar 

  36. Conforti G, Dominguez JC, Ronne E, et al: Cell-surface plasminogen activation causes a retraction of in vitro cultured human umbilical vein endothelial cell monolayer. Blood 83:994–1005, 1994.

    PubMed  CAS  Google Scholar 

  37. Corcoran ML, Hewitt RE, Kleiner DJ and Kleiner WG, S-S. MMP-2: expression, activation and inhibition. Enzyme Prot 49:7–19, 1996.

    CAS  Google Scholar 

  38. DeClerck YA, Perez N, Shimada H, et al: Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 52:701–708, 1992.

    PubMed  CAS  Google Scholar 

  39. Ellis, LM and Fidler, LI: Angiogenesis and metastasis. Eur J Cancer 32A:2451–2460, 1996.

    Article  PubMed  CAS  Google Scholar 

  40. Erkell LJ, Schirrmacher, V: Quantitative in vitro assay for tumor cell invasion through extracellular matrix or into protein gels. Cancer Res 48:6933–6937, 1988.

    PubMed  CAS  Google Scholar 

  41. Faassen AE, Schrager JA, Klein DJ, et al: A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol 116:521–531, 1992.

    Article  PubMed  CAS  Google Scholar 

  42. Fidler IJ, Kumar R, Bielenberg DR, et al Molecular determinants of angiogenesis in cancer metastasis. Cancer J Sci Am S58–66, 1998.

  43. Folkman, J: Angiogenesis and angiogenesis inhibition: an overview. Exs 79:1–8, 1997.

    PubMed  CAS  Google Scholar 

  44. Fridman R, Fuerst TR, Bird RE, et al: Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions. J Biol Chem 267:15398–15405, 1992.

    PubMed  CAS  Google Scholar 

  45. Fukushima Y, Ohnishi T, Arita N, et al: Integrin alpha3beta l-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells. Int J Cancer 76:63–72, 1998.

    Article  PubMed  CAS  Google Scholar 

  46. Ghola A, Eckert K, Maurer, HR: A rapid and sensitive fluorometric screening assay using YO-PRO-1 to quantify tumor cell invasion through matrigel. Clin Exp Metastasis 14:451–458, 1996.

    Article  Google Scholar 

  47. Giavazzi R: The nude mouse in oncology research. In: Metastatic Models (Eds: Boven, E and Winograd, B), CRC Press, Inc, London, 1991, pp. 117–132.

    Google Scholar 

  48. Giavazzi R: Cytokine-mediated tumor-endothelial cell interaction in metastasis. Curr Top Microbiol Immunol 213:13–30,1996.

    PubMed  CAS  Google Scholar 

  49. Giavazzi R, Garofalo A, Bani MR, et al: Interleukin1-induced augumentation of experimental metastases from a human melanoma in nude mice. Cancer Res 50:4771–4775, 1990.

    PubMed  CAS  Google Scholar 

  50. Giunciuglio D, Culty M, Fassina G, et al: Invasive phenotype of MCF-10A cells overexpressing c-Ha-ras and c-erb-B2 oncogenes. Int J Cancer 63:815–822, 1995.

    Article  PubMed  CAS  Google Scholar 

  51. Gomez DE, Alonso DF, Yoshiji H, et al: Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74:111–122, 1997.

    PubMed  CAS  Google Scholar 

  52. Grander, D: How do mutated oncogenes and tumor suppressor genes cause cancer? Med Oncol 15:20–26, 1998.

    Article  PubMed  CAS  Google Scholar 

  53. Grant DS, Tashiro K, Segui-Real B, et al: Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58:933–943, 1989.

    Article  PubMed  CAS  Google Scholar 

  54. Guilford P, Hopkins J, Harraway J, et al: E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405, 1998.

    Article  PubMed  CAS  Google Scholar 

  55. Harmey JH, Dimitriadis E, Kay E, et al: Regulation of macrophage production of vascular endothelial growth factor (VEGF) by hypoxia and transforming growth factor beta-1. Ann Surg Oncol 5:271–278, 1998.

    Article  PubMed  CAS  Google Scholar 

  56. Hart IR, Birch M, Marshall, JF: Cell adhesion receptor expression during melanoma progression and metastasis. Cancer Metastasis Rev 10:115–128, 1991.

    Article  PubMed  CAS  Google Scholar 

  57. Hendrix MJC, Seftor EA, Seftor REB, et al: Comparison of tumor cell invasion assay: human amnion versus reconstituted basement membrane barriers. Invas Metast 9:278–297, 1989.

    CAS  Google Scholar 

  58. Hendrix MJC, Wood WR, Seftor EA, et al: Retinoic acid inhibition of human melanoma cell invasion through a reconstituted basement membrane and its relation to decreases in the expression of proteolytic enzymes and motility factor receptor. Cancer Res 50:4121–4130, 1990.

    PubMed  CAS  Google Scholar 

  59. Hiraguri S, Godfrey T, Nakamura H, et al: Mechanisms of inactivation of E-cadherin in breast cancer cell lines. Cancer Res 58:1972–1977, 1998.

    PubMed  CAS  Google Scholar 

  60. Howe A, Aplin AE, Alahari SK, et al: Integrin signaling and cell growth control. Curr Opin Cell Biol 10:220–31, 1998.

    Article  PubMed  CAS  Google Scholar 

  61. llyas M, Tomlinson IP: The interactions of APC, E-cadherin and beta-catenin in tumour development and progression. J Pathol 182:128–137, 1997.

    Article  Google Scholar 

  62. Imamura H, Takao S, Aikou, T: A modified invasion-3(4,5-dimethylthiazole-2-yl)-2,5-diphenytetrazolium bromide assay for quantitating tumor cell invasion. Cancer Res 54:3620–3624, 1994.

    PubMed  CAS  Google Scholar 

  63. Imren S, Kohn D, Shimada H, et al: Overexpression of tissue inhibitor of metalloproteinases-2 by retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion. Cancer Res 56:2891–2895, 1996.

    PubMed  CAS  Google Scholar 

  64. Ingber D, Fujita T, Kishimoto S, et al: Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 348:555–557, 1990.

    Article  PubMed  CAS  Google Scholar 

  65. Iurlaro M, Benelli R, Masiello L, et al: Beta Interferon inhibits HIV-1 Tat induced angiogenesis; synergism with 13-cis Retinoic Acid. Eur J Cancer 34:570–576, 1998.

    Article  PubMed  CAS  Google Scholar 

  66. Jacob K, Wach F, Knuchel R, et al: Characterization of selected strongly and weakly invasive sublines of a primary human melanoma cell line and isolation of subtractive cDNA clones. Int J Cancer 60:668–675, 1995.

    Article  PubMed  CAS  Google Scholar 

  67. Jones JL, Royall JE, Critchley DR, et al: Modulation of myo-epithelial-associated alpha6beta4 integrin in a breast cancer cell line alters invasive potential. Exp. Cell Res. 235:325–333, 1997.

    Article  PubMed  CAS  Google Scholar 

  68. Joukov V, Kaipainen A, Jeltsch M, et al: Vascular endothelial growth factors VEGF-B and VEGF-C. J Cell Physiol 173:211–215, 1997.

    Article  PubMed  CAS  Google Scholar 

  69. Kannagi R: Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj J 14:577–584, 1997.

    Article  PubMed  CAS  Google Scholar 

  70. Kawada A, Hara K, Kominami E, et al: Expression of cathep-sin D and B in invasion and metastasis of squamous cell carcinoma. Br J Dermatol 137:361–366, 1997.

    Article  PubMed  CAS  Google Scholar 

  71. Keski OJ, Lohi .J, Tuuttila A, et al: Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202:471–476, 1992.

    Article  Google Scholar 

  72. Khokha R, Zimmer MJ, Graham CH, et al: Suppression of invasion by inducible expression of tissue inhibitor of metal-loproteinase-1 (TIMP-1) in B16-F10 melanoma cells. J. Natl Cancer Inst 84:1017–1022, 1992.

    Article  PubMed  CAS  Google Scholar 

  73. Kim J, Yu W, Kovalski K, et al: Requirement for specific proteases in cancer cell intravasation as revealed by a novel semi-quantitative PCR-based assay. Cell 94:353–362, 1998.

    Article  PubMed  CAS  Google Scholar 

  74. Klein S, Roghani M, Rifkin, DB: Fibroblast growth factors as angiogenesis factors: new insights into their mechanism of action. Exs 79:159–192, 1997.

    PubMed  CAS  Google Scholar 

  75. Kleinman HK, McGarvey ME, Hassell JR, et al: Basement membranes complexes with biological activity. Biochemistry 25:312–318, 1986.

    Article  PubMed  CAS  Google Scholar 

  76. Knutson JR, J. Lidia, Fields, GB, McCarthy, JB: CD44/ chon-droitin sulfate proteoglycan and alpha2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes. Mol Biol Cell 7:383–396, 1996.

    PubMed  CAS  Google Scholar 

  77. Kohn EC, Liotta, LA: Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res 55:1856–1862, 1995.

    PubMed  CAS  Google Scholar 

  78. Kubota S, Ito H, Ishibashi Y, et al: Anti-alpha3 integrin antibody induces the activated form of matrix metalloprotease-2 (MMP-2)with concomitant simulation of invasion through matrigel by human rhabdomyosarcoma cells. Int J Cancer 70:106–111, 1997.

    Article  PubMed  CAS  Google Scholar 

  79. Kusama T, Nakamori S, Ohigashi H, et al: Enhancement of in vitro tumor-cell transcellular migration by tumor- cell-secreted endothelial-cell-retraction factor. Int J Cancer 63:112–118, 1995.

    Article  PubMed  CAS  Google Scholar 

  80. Lawrence JA, Steeg PS: Mechanisms of tumor invasion and metastasis. World J Urol 14:124–130, 1996.

    Article  PubMed  CAS  Google Scholar 

  81. Leek RD, Lewis CE, Whitehouse R, et al: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625–4629, 1996.

    PubMed  CAS  Google Scholar 

  82. Levine MD, Liotta LA, Stracke, ML: Stimulation and regulation of tumor cell motility in invasion and metastasis. Exs 74:157–179, 1995.

    PubMed  CAS  Google Scholar 

  83. Li J, Hu SX, Perng GS, et al: Expression of the retinoblastoma (RB) tumor suppressor gene inhibits tumor cell invasion in vitro. Oncogene 13:2379–2386, 1996.

    PubMed  CAS  Google Scholar 

  84. Lindauer M, Stanislawski T, Haussier A, et al: The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes. J Mol Med 76:32–47, 1998.

    Article  PubMed  CAS  Google Scholar 

  85. Liotta L, Steeg P, Stetler-Stevenson, W: Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64:327–336, 1991.

    Article  PubMed  CAS  Google Scholar 

  86. Liotta LA: Tumor invasion and metastases - Role of the extracellular matrix: Rhoads memorial award lecture. Cancer Res. 46:1–7, 1986.

    PubMed  CAS  Google Scholar 

  87. Luca M, Huang S, Gershenwald JE, et al: Expression of Interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151:1105–1113, 1997.

    PubMed  CAS  Google Scholar 

  88. Maggiora P, Gambarotta G, Olivero M, et al: Control of invasive growth by the HGF receptor family. J Cell Physiol 173:183–186, 1997.

    Article  PubMed  CAS  Google Scholar 

  89. Mareel M, Boterberg T, Noe V, et al: E-Cadherin/Catenin/Cy-toskeleton complex: a regulator of cancer invasion. J Cell Physiol 173:271–274, 1997.

    Article  PubMed  CAS  Google Scholar 

  90. Matrisian LM, Ganser GL, Kerr LD, et al: Negative regulation of gene expression by TGF-beta. Mol Reprod Dev 32:111–120, 1992.

    Article  PubMed  CAS  Google Scholar 

  91. Maurer CA, Friess H, Kretschmann B, et al: Over-expression of ICAM-1, VCAM-1 and ELAM-1 might influence tumor progression in colorectal cancer. Int J Cancer 79:76–81, 1998.

    Article  PubMed  CAS  Google Scholar 

  92. Mazzieri R, Masiero L, Zanetta L, et al: Control of type IV collagenase activity by components of the urokinase- plasmin system: a regulatory mechanism with cell-bound reactants. Embo J 16:2319–232, 1997.

    Article  PubMed  CAS  Google Scholar 

  93. Meade TL, Boukamp P, Fusenig NE, et al: Differential expression of matrix metalloproteinases in activated c-ras- Ha-trans- fected immortalized human keratinocytes. Br J Cancer 77:724–730, 1998.

    Google Scholar 

  94. Melchiori A, Albini A, Ray JM, et al: Inhibition of tumor cell invasion by a highly conserved peptide sequence from the matrix metalloproteinase enzyme prosegment. Cancer Res 52:2353–2356, 1992.

    PubMed  CAS  Google Scholar 

  95. Melchiori A, Car lone S, Allavena G, et al: Invasiveness and chemotactic activity of oncogene transformed NIH/3T3 cells. Anticancer Res 10:37–44, 1990.

    PubMed  CAS  Google Scholar 

  96. Melchiori A, Mortarini R, Carlone S, et al: The α3β1 integrin is involved in melanoma cell migration and invasion. Exp Cell Res 218:233–242, 1995.

    Article  Google Scholar 

  97. Merzak A, Koocheckpour S, Pilkington, GJ: CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res 54:3988–3992, 1994.

    PubMed  CAS  Google Scholar 

  98. Mignatti P, Rifkin, DB: Plasminogen activators and matrix metalloproteinases in angiogenesis. Enzyme Protein 49:117–137, 1996.

    PubMed  CAS  Google Scholar 

  99. Natali PG, Nicotra MR, Bartolazzi A, et al: Integrin expression in cutaneous malignant melanoma: association of the alpha 3/beta 1 heterodimer with tumor progression. Int J Cancer 54:68–72, 1993.

    Article  PubMed  CAS  Google Scholar 

  100. O’Reilly MS, Boehm T, Shing Y, et al: Endostatin: an endoge- nous inhibitor of angiogenesis and tumor growth. Cell 88:277–285, 1997.

    Article  PubMed  CAS  Google Scholar 

  101. O’Reilly MS, Holmgren L, Chen C, et al: Angiostatin induces and sustains dormancy of human primary tumors in mice. Nature Med 2:689–692, 1996.

    Article  PubMed  CAS  Google Scholar 

  102. Oft M, Peli J, Rudaz C, et al: TGF-betal and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10:2462–2477, 1996.

    Article  PubMed  CAS  Google Scholar 

  103. Ohtani H: Stromal reaction in cancer tissue: pathophysiologic significance of the expression of matrix-degrading enzymes in relation to matrix turnover and immune/inflammatory reactions. Pathol Int 48:1–9, 1998.

    PubMed  CAS  Google Scholar 

  104. Perl AK, Wilgenbus P, Dahl U, et al: A casual role for E-cad-herin in the transition from adenoma to carcinoma. Nature 392:190–193, 1998.

    Article  PubMed  CAS  Google Scholar 

  105. Pluda JM: Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. Semin Oncol 24:203–218, 1997.

    PubMed  CAS  Google Scholar 

  106. Polverini PJ: Role of the macrophage in angiogenesis-depen-dent diseases. In: Regulation of Angiogenesis (Eds: Goldberg, IP and Rosen, ER), Birkhäuser Verlag, Basel, 1997, pp.11–28.

    Google Scholar 

  107. Price JT, Bonovich MT, Kohn EC: The biochemistry of cancer dissemination. Crit Rev Biochem Mol Biol 32:175–253, 1997.

    Article  PubMed  CAS  Google Scholar 

  108. Qian F, Vaux DL, Weissman IL: Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell 77:335–347, 1994.

    Article  PubMed  CAS  Google Scholar 

  109. Rabinovitz I, Mercurio AM: The integrin alpha 6 beta 4 and the biology of carcinoma. Biochem Cell Biol 74:811–21, 1996.

    PubMed  CAS  Google Scholar 

  110. Radotra B, McCormick D: Glioma invasion in vitro is mediated by CD44-hyaluronan interactions. J Pathol 181:434–438, 1997.

    Article  CAS  Google Scholar 

  111. Ramos MA, Kuzuya M, Esaki T et al: Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. Arterioscler Thromb Vase Biol 18:1188–1196, 1998.

    CAS  Google Scholar 

  112. Ray JM, Stetler SW: The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis. Eur Respir J 7:2062–2072, 1994.

    PubMed  CAS  Google Scholar 

  113. Ray JM, Stetler-Stevenson WG: Gelatinase A activity directly modulates melanoma cell adhesion and spreading. EMBO J 14:908–917, 1995.

    PubMed  CAS  Google Scholar 

  114. Repesh LA: A new in vitro assay for quantitating tumor cell invasion. Invas Metast 9:192–208, 1989.

    CAS  Google Scholar 

  115. Ries C, Petrides PE: Cytokine regulation of matrix metalloproteinase activity and its regulatory dysfunction in disease. Biol Chem Hoppe Seyler 376:345–355, 1995.

    PubMed  CAS  Google Scholar 

  116. Ruoslahti E: Integrins as signaling molecules and targets for tumor therapy. Kidney Int 51:1413–1417, 1997.

    Article  PubMed  CAS  Google Scholar 

  117. Saito K, Oku T, Ata N, et al: A modified and convenient method for assessing tumor cell invasion and migration and its application to screening for inhibitors. Biol Pharm Bull 20:345–348, 1997.

    PubMed  CAS  Google Scholar 

  118. Sasaki CY, Passaniti, A: Identification of anti-invasive but noncytotoxic chemotherapeutic agents using the tetrazolium dye MTT to quantitate viable cells in matrigel. Biotechniques 24:1038–1043, 1998.

    PubMed  CAS  Google Scholar 

  119. Sato H, Okada Y, Seiki M: Membrane-type matrix metallo-prteinases (MT-MMPs) in cell invasion. Thromb Haemost 78:497–500, 1997.

    PubMed  CAS  Google Scholar 

  120. Sato H, Takino T, Okada Y, et al: A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370:61–65, 1994.

    Article  PubMed  CAS  Google Scholar 

  121. Schonermark MP, Bock O, Buchner A, et al: Quantification of tumor cell invasion using confocal laser scan microscopy. Nat Med 3:1167–1171, 1997.

    Article  PubMed  CAS  Google Scholar 

  122. Seftor EA, Seftor RE, Hendrix MJ: Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. Biotechniques 9:324–331, 1990.

    PubMed  CAS  Google Scholar 

  123. Siegal GP, Wang MH, Rinehart CA, et al: Development of a novel human extracellular matrix for quantitation of invasive-ness of human cells. Cancer Lett. 69:123–132, 1993.

    Article  PubMed  CAS  Google Scholar 

  124. Smith SK: Angiogenesis. Semin Reprod Endocrinol 15:221–227, 1997.

    Article  PubMed  CAS  Google Scholar 

  125. St Croix B, Sheehan C, Rak JW, et al: E-Cadherin-dependent growth suppression is mediated by the cyclin- dependent kinase inhibitor p27(KIP1). J Cell Biol 142:557–571, 1998.

    Article  Google Scholar 

  126. Stetler-Stevenson M, Mansoor A, Lim M, et al: Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells. Blood 89:1708–1715, 1997.

    PubMed  CAS  Google Scholar 

  127. Stetler-Stevenson W, Hewitt R, Corcoran M. Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin Cancer Biol 7:147–154, 1996.

    Article  PubMed  CAS  Google Scholar 

  128. Stetler-Stevenson WG, Corcoran ML: Tumor angiogenesis: functional similarities with tumor invasion. EXS 79:413–418, 1997.

    PubMed  CAS  Google Scholar 

  129. Stoppelli MP, Corti A, Soffientini A, et al: Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes. Proc Natl Acad Sci U S A 82:4939–4943, 1985.

    Article  PubMed  CAS  Google Scholar 

  130. Talbot DC, Brown PD: Experimental and clinical studies on the use of matrix metalloproteinase inhibitors for the treatment of cancer. Eur J Cancer 32:2528–2533, 1996.

    Article  Google Scholar 

  131. Taraboletti G, Garofalo A, Belotti D, et al: Inhibition of angiogenesis and murine hemangioma growth by batimastat, a synthetic inhibitor of matrix metalloproteinases. J Natl Cancer Inst 87:293–298, 1995.

    Article  PubMed  CAS  Google Scholar 

  132. Terman BI, Dougher VM: Biological properties of VEGF/VPF receptors. Cancer Metastasis Rev 15:159–163, 1996.

    Article  PubMed  CAS  Google Scholar 

  133. Thompson E, Nakamura S, Shima T et al: Supernatants of acquired immunodeficiency syndrome-related Kaposi’s sarcoma cells induce endothelial cell chemotaxis and invasiveness. Cancer Res. 51:2670–2671, 1991.

    PubMed  CAS  Google Scholar 

  134. Timar J, Raso E, Fazakas Zs, et al: Multiple use of a signal transduction pathway in tumor cell invasion. Anticancer Res 16:3299–3306, 1996.

    PubMed  CAS  Google Scholar 

  135. Tryggvason K, Hoyhtya M, Pyke, C: Type IV collagenases in invasive tumors. Breast Cancer Res Treat 24:209–218, 1993.

    Article  PubMed  CAS  Google Scholar 

  136. Tsai V, Kawashima I, Keogh E, et al: In vitro immunization and expansion of antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy using peptide-pulsed dendritic cells. Crit Rev Immunol 18:65–75, 1998.

    PubMed  CAS  Google Scholar 

  137. Valente P, Fassina GF, Melchori A, et al: TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis. Int J Cancer 75:246–253, 1998.

    Article  PubMed  CAS  Google Scholar 

  138. Valente P, Melchiori A, Paggi MG, et al: Rb-1 oncosuppressor gene over-expression inhibits tumour progression and induces melanogenesis in metastatic melanoma cells. Oncogene 13:1169–1178, 1996.

    PubMed  CAS  Google Scholar 

  139. Woodhouse EC, Chuaqui RF, Liotta LA: General mechanisms of metastasis. Cancer 80:1529–1537, 1997.

    Article  PubMed  CAS  Google Scholar 

  140. Wright JA, Huang A: Growth factors in mechanisms of malignancy: roles for TGF-beta and FGF. Histol Histopathol 11:521–536, 1996.

    PubMed  CAS  Google Scholar 

  141. Xie S, Luca M, Huang S, et al: Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 57:2295–2303, 1997.

    PubMed  CAS  Google Scholar 

  142. Xiong M, Elson G, Legarda D, et al: Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway. Am J Pathol 153:587–598, 1998.

    PubMed  CAS  Google Scholar 

  143. Xue W, Mizukami I, Todd RF, et al: Urokinase-type plasmino-gen activator receptors associate with betal and beta3 inte-grins of fibrosarcoma cells: dependence on extracellular matrix components. Cancer Res 57:1682–1689, 1997.

    PubMed  CAS  Google Scholar 

  144. Yamamoto H, Irie V, Fukushima Y, et al: Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin alpha6 subunit expression. Int J Cancer 65:519–524, 1996.

    Article  PubMed  CAS  Google Scholar 

  145. Yu AE, Hewitt RE, Kleiner DE, et al: Molecular regulation of cellular invasion—role of gelatinase A and TIMP-2. Biochem Cell Biol 74:823–31, 1996.

    Article  PubMed  CAS  Google Scholar 

  146. letter BR: Adhesion molecules in tumor metastasis. Semin Cancer Biol 4:219–229, 1993.

    Google Scholar 

  147. Zetter BR: Angiogenesis and tumor metastasis. Annu Rev Med 49:407–424, 1998.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Adriana Albini.

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Albini, A. Tumor and endothelial cell invasion of basement membranes. Pathol. Oncol. Res. 4, 230–241 (1998). https://doi.org/10.1007/BF02905254

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