THE ROLE OF CCL21/CCR7 CHEMOKINE AXIS IN VEGF-C MEDIATED BREAST CANCER INDUCED LYMPHANGIOGENESIS

Although the molecular mechanisms underlying lymphangiogenesis associated with breast cancer continue to remain insufficiently understood, a growing body of evidence suggests that many of the currently unknown answers revolve around the crosstalk between the lymphangiogenic factor VEGF-C and chemokines. The present study proposed the CCL21/CCR7 chemokine axis as a regulatory mechanism of VEGF-C mediated breast cancer-induced lymphangiogenesis. In order to address the hypothesis, the positive correlations between CCR7 signalling and VEGF-C expression/secretion by MDA-MB-231 cells were sought, along with the molecular mechanism underlying their correlation. Furthermore, the direct effect of CCL21/CCR7 interaction on lymphatic endothelial cells (LECs) was tested through a series of in vitro lymphangiogenic assays. CCL21/CCR7 axis has been found to regulate lymphangiogenesis in two distinct ways: i) directly, through stimulation of the lymphangiogenic traits of LECs; and ii) indirectly, through the promotion of VEGF-C secretion by breast cancer cells. These results suggest a novel role of the CCL21/CCR7 axis in the promotion of breast cancer-induced lymphangiogenesis