Abstract 534: Tumor-associated endothelial cells promote tumor metastasis by chaperoning circulating tumor cells and protecting them from anoikis
Authors: Bhavna Kumar, Arti Yadav, Theodoros N. Teknos, Pawan Kumar
Journal: Cancer Research (2011)

Abstract Metastatic spread of tumor cells to vital organs is the major cause of mortality in cancer patients. Tumor metastasis is a complex process involving multiple steps including detachment of tumor cells from the primary tumor, interaction with vascular endothelium and invasion of target organs. Although our understanding of the molecular and biological events that contribute to tumor cell progression has increased considerably over the last decade, we still know very little about the role of tumor-accessory cells in promoting tumor cell release from the primary tumor and metastasis to distal sites. It is well established that tumor angiogenesis plays a critical role in tumor progression. We have recently demonstrated that VEGF, in addition to its pro-angiogenic function, also induces the expression of Bcl-2 in the microvascular endothelial cells. Furthermore, tumor samples from head and neck cancer patients showed significantly higher Bcl-2 expression in tumor blood vessels and this enhanced Bcl-2 expression in tumor-associated endothelial cells was directly correlated with metastatic status of these patients. In addition, blood samples from head and neck cancer patients showed significantly higher Bcl-2 positive circulating endothelial cells. What role these circulating Bcl-2 positive endothelial cells play is not known. In this study, we performed a series of experiments to examine if tumor-associated endothelial cells could promote tumor cell metastasis by chaperoning these tumor cells to distal sites. Our results demonstrate that endothelial cells overexpressing Bcl-2 (EC-Bcl-2) show significantly higher E-selectin expression and exhibit enhanced tumor cell binding. In addition, tumor cells (UM-SCC-74A) showed a significant decrease in anoikis when co-cultured with EC-Bcl-2 in non-adherent conditions. This anoikis resistance in tumor cell bound to endothelial cells was mediated by the activation of FAK survival signaling. We further examined the role of Bcl-2 in tumor cell metastasis using two SCID mice models. In the first model, tumor cells were co-implanted with EC-Bcl-2 or EC-VC in the flanks of SCID mice. Tumor cells when co-implanted with EC-Bcl-2 showed significantly higher lung metastasis as compared to EC-VC group. Interestingly, lung samples from these animals showed the presence of EC-Bcl-2 cells (GFP-labeled, primary tumor origin) in the metastatic nodes. In the second in vivo model, tumor cells were injected via the tail vein either alone or along with EC-Bcl-2 or EC-VC. Animals co-injected with tumor cells and EC-Bcl-2 showed significantly higher lung metastasis as compared to tumor cell and EC-VC or tumor cell alone group. Taken together, these results suggest a novel role for tumor-associated endothelial cells in binding to tumor cells, protecting them from anoikis and chaperoning them to distal sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 534. doi:10.1158/1538-7445.AM2011-534