E32 Tumor angiogenesis

Topic

Angiogenesis is the formation of new blood vessels in response to signals emitted by the tumor itself. Without angiogenesis, the tumor cannot grow beyond a limit of approximately one to two millimeters—the same limit imposed by the oxygen diffusion radius from host tissue vessels.

Angiogenesis acts as a switch regarding this limit: once activated, it unlocks tumor growth far beyond that one-to-two-millimeter threshold, allowing the tumor to reach a macroscopic size.

However, the very angiogenesis that enables macroscopic tumor growth simultaneously creates an abnormal vasculature; paradoxically, this abnormal vasculature gives rise to three new problems: hypoxia within the tumor itself, elevated pressure within the tumor tissue, and drug resistance.

The physics underlying this process involves chemical gradients and vascular chemotaxis: when hypoxic, the tumor secretes a signaling protein that stimulates blood vessel formation. This protein creates a concentration gradient—higher near the tumor and lower further away—towards which the new blood vessels grow.

The tumor vasculature resulting from this gradient-driven growth is functionally deficient: the vessels are dilated and permeable, lack the cells that normally envelop and stabilize blood vessels, and exhibit irregular blood flow that can even reverse direction. Thus, the very angiogenesis that allows the tumor to overcome the diffusion limit and grow to a macroscopic size also leaves it with a vasculature far inferior to that of the surrounding healthy tissue.

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