ROLE OF THE GUT VASCULAR BARRIER IN METASTATIC COLON CANCER

Spreading of neoplastic cells from colon cancer to regional lymph nodes (LN) is often associated with distant recurrence. However, a number of clinical trials have shown that lymphadenectomy is not increasing Colon Cancer (CC) patient’s survival. This phenomenon is probably due to a metastatic dissemination that occurs via the systemic blood circulation, rather than the lymphatic vessels. How such dissemination is achieved is unknown. We hypothesized that the disruption of the vasculature in colon tumors can be linked to cancer cells dissemination. We identified a new marker of deranged vasculature which is expressed in primary tumors of CC patients that have developed metachronous distant metastases, independently from the presence of metastases in regional LN. Moreover, we studied vasculature disruption in a mouse model that develops spontaneous tumors mainly in the colon. These mice showed dismantled vasculature at tumor level and they concomitantly exhibited the formation of a pre-metastatic niche at distant sites which favored the recruitment of metastatic cells. Vascular impairment can shed light on the process of colon metastases and this new marker can be used as a prognostic marker for distant recurrence.