Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis

doi:10.1016/0026-2862(77)90141-8

Microvascular Research

Volume 14, Issue 1, July 1977, Pages 53-65

https://doi.org/10.1016/0026-2862(77)90141-8 Get rights and content

Abstract

Tumor-induced capillary proliferation was studied in the rabbit cornea after implantation of V2 carcinoma 1 mm from the limbal vascular plexus. Limbal vessels were examined 1 to 10 days later with: [³H]thymidine autoradiography, electron microscopy, intravenous injection of colloidal carbon, and slit-lamp stereomicroscopy. Endothelial cells displayed surface projections and resembled regenerating endothelium 1 day after tumor implant. At 2 days, cells emigrated from preformed vessels toward the tumor implant. Simultaneously, cell junctions loosened and new lumina appeared in the walls of existing venules. Capillary sprouts were detected histologically at Day 4 and entered the corneal stroma by Day 6. New vessels were never seen in control eyes implanted with heat-killed tumor. The thymidine labeling index of endothelium was elevated on Day 2 and reached a peak of 8% on Day 3. After Day 4, labeled cells were located only near the distal tips of the growing capillaries. The labeling index ranged from 0.6 to 4%. In controls, labeling was less than 0.7% after 3 days.

These studies suggest that active migration of preformed endothelial cells toward the tumor stimulus may precede cell proliferation during tumor angiogenesis. Whether this sequence occurs in other forms of neovascularization is unknown. However, once new capillaries have appeared, tumor-induced vessels elongate by mechanisms similar to wound-induced capillaries.

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^☆: A preliminary report of this work was presented at the 89th Annual Meeting of the American Association of Anatomists in Louisville, Kentucky, in April 1976.

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Microvascular Research

Abstract

References (23)

Increased endothelial cell turnover in areas of in vivo Evans blue uptake in the pig aorta

Atherosclerosis

Limbal vascular response prior to corneal vascularization

Exp. Eye Res

Human vascular endothelial cells in culture

Lack of response to serum growth factors

Exp. Cell Res

Tumor angiogenesis: Rapid induction of endothelial mitoses demonstrated by autoradiography

J. Cell Biol

Observations on healing tissue: A combined light and electron microscopic investigation

Trans. Roy. Soc. London Ser. B

Cell turnover of capillaries

Lab. Invest

Tumor angiogenesis

Relation of vascular proliferation to tumor growth

Isolation of a tumor factor responsible for angiogenesis

J. Exp. Med

Tumor growth and neovascularization: An experimental model using the rabbit cornea

J. Nat. Cancer Inst

Autoradiographic and ultrastructural observations on the frog's olfactory mucosa

Z. Zellforsch. Mikrosk. Anat

Cited by (1094)

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Multi-scale model of lumen formation via inverse membrane blebbing mechanism during sprouting angiogenesis process

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Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis☆

Abstract

Atherosclerosis

Exp. Eye Res

Exp. Cell Res

Tumor angiogenesis: Rapid induction of endothelial mitoses demonstrated by autoradiography

J. Cell Biol

Observations on healing tissue: A combined light and electron microscopic investigation

Trans. Roy. Soc. London Ser. B

Cell turnover of capillaries

Lab. Invest

Tumor angiogenesis

Relation of vascular proliferation to tumor growth

Isolation of a tumor factor responsible for angiogenesis

J. Exp. Med

Tumor growth and neovascularization: An experimental model using the rabbit cornea

J. Nat. Cancer Inst

Autoradiographic and ultrastructural observations on the frog's olfactory mucosa

Z. Zellforsch. Mikrosk. Anat