Ets-1 drives breast cancer cell angiogenic potential and interactions between breast cancer and endothelial cells

Furlan,Alessandro; Vercamer,Chantal; Heliot,Laurent; Wernert,Nicolas; Desbiens,Xavier; Pourtier,Albin

doi:10.3892/ijo.2018.4605

Ets-1 drives breast cancer cell angiogenic potential and interactions between breast cancer and endothelial cells

Authors:
- Alessandro Furlan
- Chantal Vercamer
- Laurent Heliot
- Nicolas Wernert
- Xavier Desbiens
- Albin Pourtier
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Affiliations: UMR8161 CNRS/University of Lille/Pasteur Institute of Lille, Biology Institute of Lille, F-59021 Lille CEDEX, France, UMR8523 PhLAM, CNRS/University of Lille, 59655 Villeneuve d'Ascq CEDEX, France, Institute of Pathology, University of Bonn, 53011 Bonn, Germany
Published online on: October 24, 2018 https://doi.org/10.3892/ijo.2018.4605
Pages: 29-40
Copyright: © Furlan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ets-1 transcription factor overexpression in breast cancers is associated with invasive features and is associated with a poor prognosis. Beyond its role in driving carcinoma cell invasion, in this study, we wished to determine whether Ets-1 overexpression in cancer cells promotes angiogenesis by creating a paracrine pro-invasive environment for endothelial cells as well. To address this question, we set up different co-culture models of cancer cells with endothelial cells. Conditioned media from cancer cells induced endothelial cell proliferation, migration and morphogenesis in matrix models. Of note, co-culture assays in three-dimensional matrix models also revealed the reciprocal induction of cancer cell morphogenesis by endothelial cells, in support of an angiocrine action on tumor cells. Ets-1 emerged as a key regulator of the angiogenic potential of breast cancer cells, favoring their ability to induce, in a paracrine manner, the morphogenesis of endothelial cells and also to physically interact with the latter. Nevertheless, Ets-1 overexpression in cancer cells also restrained their chemoattractive potential for endothelial cells both in Boyden chambers and in ex vivo 3D co-cultures. Finally, Ets-1 modulation in breast cancer cells qualitatively altered the angiogenic pattern of experimental in vivo tumors, with a balance between vessel recruitment and intratumoral small capillaries sprouting. Taken together, our data highlight a critical and intriguing role for Ets-1 in the angiogenic potential of breast cancer cells, and reveal another facet of Ets-1 oncogenic activities.

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