Tapasree Roy Sarkar

The University of Texas MD Anderson Cancer Center, USA

Title: EMT-induced carcinoma cells can differentiate into endothelial cells and contribute to tumor growth

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Biography

She received her PhD degree from Purdue University. Then she did her postdoctoral research at National Cancer Institute/National Institute of health (supervised by Dr. Esta Sterneck) and University of Texas M.D. Anderson Cancer center (Supervised by Dr. Sendurai Mani). After her postdoctoral work she joined Department of Biology at Texas A&M University as a faculty. She has published more than 21 research articles in reputed journals such as PNAS, Oncogene, Cancer research, Oncotarget etc. 

Abstract

Hypoxia stimulates angiogenesis, promotes tumor growth, and triggers the epithelial-mesenchymal transition (EMT), which bestows cells with mesenchymal traits and multi-lineage differentiation potential. In this study, we investigated whether EMT can confer endothelial attributes upon carcinoma cells, augmenting tumor growth and vascularization. Human epithelial breast cancer cells (MCF7) were orthotopically injected into mice. The tumors of different sizes were harvested and immunostained for markers of hypoxia and EMT. Larger tumors were found to be well-vascularized with CD31-positive cells of human origin. It was observed that hypoxic regions in the tumors (demarcated by HIF-1? staining), exhibited E-cadherin loss and elevated levels of mesenchymal markers such as vimentin and FOXC2. When MCF-7 cells were implanted, co-mixed with human mammary epithelial (HMLE) cells overexpressing the EMT-inducer Snail, markedly potentiated tumor growth and vascularization, compared with MCF-7 cells injected alone or co-mixed with HMLE-vector cells. Intra-tumoral vessels contained CD31-positive cells derived from either donor cell type which indicated the mesenchymal to endothelial transdifferentiattion. FOXC2 knockdown was found to abrogate the potentiating effects of HMLE-Snail cells on MCF-7 tumor growth and vascularization, and compromised endothelial transdifferentiation. Therefore, we concluded cells that have undergone EMT can promote tumor growth and neovascularization by promoting endothelial transdifferentiation of carcinoma cells, with FOXC2 playing key roles in these processes. This complex mechanism underlying neoangiogenesis differ from physiological angiogenesis and lead to the formation of dysfunctional and disorganized vessels with a defective endothelial layer, which nevertheless fuels tumor progression. This mechanism along with vascular mimicry are involved in the anti-angiogenesis therapy resistance.