Dominion Pharmakine has just published in the January-1 issue of Cancer Research journal (see Mendoza et al, Cancer Res 2004; 64(1): 304-310) data on the company's discovery that inhibition of cytokine-induced microvascular arrest of tumor cells by recombinant endostatin prevents experimental hepatic melanoma metastasis.

The capillary arrest of circulating cancer cells at target organs constitutes an early stage of the metastasis process that precedes proliferation of cancer cells along an angiogenesis-dependent mechanism. It is well-known that proinflammatory cytokine-induced cell adhesion molecules play a role in this microvascular phase of metastasis. This study shows for the first time the ability of endostatin to abrogate proinflammatory cytokine production from endothelial cells activated by melanoma-derived vascular endotelial growth factor (VEGF). In turn, this deactivates the prometastatic microenvironment of tumor-induced inflammation and prevents progression of metastatic disease.

The study evidences that endostatin's tumor inhibitory capabilities include mechanisms other than those directly affecting angiogenic endothelial cells per se such as apoptosis, migration, and proliferation. In addition, these results may have a broader significance if we consider that as the expression of VEGF increases, the probability of metastasis also increases in most of human malignant tumors. Thus, administration of endostatin to patients bearing VEGF-overexpressing tumors at high risk of progression may also help in preventing metastasis. Other candidate patients may be those surgically treated from primary tumor with no lymph node involvement but having detectable levels of circulating cancer cells.
These data suggests a new direction for better understanding of the biology of this endogenous product of collagen XVIII cleavage. The fact that endostatin potently affects the powerful arm of the inflammatory response induced by VEGF implies that endostatin's clinical efficacy extends beyond angiostatic properties.