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• The angiogenic process

The angiogenic process

A critical process for new cell and tissue growth

Angiogenesis, a key step in tumor growth and spread, is a biological process with multiple components. First, existing vasculature becomes permeable and dilated. Next, the extracellular matrix is degraded, followed by proliferation and migration of endothelial cells. Finally, support cells such as pericytes are recruited.²

Reprinted with permission of Sturk C, Dumont D. In: Tannock IF, Hill RP, Bristow RG, et al, eds. Basic Science of Oncology. 4th ed. New York, NY: McGraw-Hill; 2005:231-248.

An adequate supply of oxygen and nutrients is critical for homeostasis of virtually all human cells and tissues. This delivery of oxygen and nutrients—and the corresponding elimination of metabolic waste and carbon dioxide—are dependent on the vascular system. Accordingly, the formation of new tissue is systematically coordinated with the formation of a new vasculature. In this process, endothelial cells (the primary building blocks of vasculature) must undergo 4 major steps.²

The 4 major steps of endothelial cells in angiogenesis

1. Breaking through of the basal lamina that envelopes existing blood vessels

2. Migration toward a source signal

3. Proliferation

4. Formation of tubes

Like most processes in homeostatic cellular systems, angiogenesis is a complex, highly regulated system. A large number of pro-angiogenic growth factors have been identified, many of which are capable of inducing all 4 of the above steps. One of the primary factors among these is a protein known as VEGF.²

Providing tumors the blood supply needed to survive…and to thrive

Angiogenesis is a vital process in the progression of cancer from small, localized neoplasms to larger, growing, and potentially metastatic tumors. To grow beyond 1 to 2 mm in diameter, a tumor needs an independent blood supply, which is acquired by expressing growth factors that recruit new vasculature from existing blood vessels. This process continues even as the tumor matures. Thus, upregulation of angiogenesis is a key step in sustained tumor growth and may also be critical for tumor metastasis.^3-6

Pathologic angiogenesis⁶

To grow beyond 1 to 2 mm in diameter, a tumor needs an independent blood supply, which is acquired by expressing growth factors that recruit new vasculature from existing blood vessels. This process continues even as the tumor matures.

Angiogenesis has been correlated with disease progression and/or poor prognosis in many tumor types—including lung, colon, breast, renal, and other cancers—and can be activated at different stages of tumor development, depending on the tumor type and microenvironmental conditions.^3-6

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References:

1.

Hanahan D, Weinberg RA. Cell. 2000;100:57-70.

2.

Sturk C, Dumont D. In: Tannock IF, Hill RP, Bristow RG, et al, eds. Basic Science of Oncology. 4th ed. New York, NY: McGraw-Hill; 2005:231-248.

3.

Ferrara N. Endocr Rev. 2004;25:581-611.

4.

Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027.

5.

Ferrara N, Hillan KJ, Gerber HP, Novotny W. Nat Rev Drug Discov. 2004;3:391-400.

6.

Bergers G, Benjamin LE. Nat Rev Cancer. 2003;3:401-410.