Abstract A06: The role of the epidermal growth factor receptor (EGFR) in primary tumor cell escape and development of an intravasation-sustaining vasculature

In this study, we investigated the specific roles of EGFR in the early steps of tumor metastasis such as escape of cancer cells from the primary tumor and development of angiogenic vasculature, the two critical events required for tumor cell intravasation. For this purpose we employed the EGFR-overexpressing highly disseminating variant of human fibrosarcoma HT-1080 cell line, HT-hi/diss, in several independent in vivo CAM models. In the spontaneous metastasis model, siRNA silencing of EGFR significantly reduced the levels of HT-hi/diss intravasation, suggesting a role of EGFR overexpression in tumor cell escape and/or development of intravasation-sustaining vasculature. We have demonstrated that EGFR silencing prevented HT-hi/diss cell escape from the primary microtumors in the intramesodermal model, linking EGFR-regulated cell motility to tumor cell intravasation. We further investigated the role of EGFR in development of tumor-associated vasculature. By using our newly developed topical microtumor model, we have demonstrated that both control and EGFR-silenced cells attract comparable numbers of angiogenic vessels converging to developing primary microtumors. However, epifluorescence microscopy revealed dramatic difference in the microarchitecture of blood vessels within the two types of microtumors. Whereas control microtumors exhibited well-developed networks of intratumoral blood vessels with lumen diameter of 15-30 µm, EGFR-silenced microtumors contained only thin blo...

Source: Cancer Research - January 12, 2015 Category: Cancer & Oncology Authors: Minder, P., Deryugina, E. I., Quigley, J. P. Tags: Tumor-Associated Blood Vessels and Lymphatics Source Type: research