Tumour-endothelial cell communications: important and indispensable mediators of tumour angiogenesis

Angiogenesis is an essential aspect of tumour growth and metastasis. Solid tumours cannot grow beyond 23 mm in diameter without inducing the formation of new blood vessels to support the energetic requirements of tumour cells. Angiogenesis is stimulated by cancer cells through a wide variety of cell-to-cell communication means. Cancer cells can induce endothelial changes by directly targeting cells via soluble factors, adhesion receptors, gap junctions and vesicles. They also can stimulate endothelial signaling pathways in an indirect way, e.g. by activating stromal cells, by secreting proteases into the extracellular space or even by changing the pH, temperature and availability of oxygen and nutrients. Anti-angiogenic drugs appear to be an effective cancer treatment in animal models but have been shown to have a limited effect in the long term. Resistance to anti-angiogenic therapies has been attributed to the ability of cancer cells to induce angiogenesis in a different way. We propose that cancer cells also change the way they communicate with endothelial cells in order to escape therapies that inhibit angiogenesis and that a better knowledge of this phenomenon will help us design more efficient drugs.