Akt-activated endothelium promotes ovarian cancer proliferation through notch activation

Jessica Hoarau, Cyril Touboul, Najeeb Halabi, Morgane Blot-Dupin, Raphael Lis, Charbel Abi Khalil, Shahin Rafii, Arash Rafii Tabrizi, Jennifer Pasquier

Research output: Contribution to journalArticle

Abstract

Background: One main challenge in ovarian cancer rests on the presence of a relapse and an important metastatic disease, despite extensive surgical debulking and chemotherapy. The difficulty in containing metastatic cancer is partly due to the heterotypic interaction of tumor and its microenvironment. In this context, evidence suggests that endothelial cells (EC) play an important role in ovarian tumor growth and chemoresistance. Here, we studied the role of tumor endothelium on ovarian cancer cells (OCCs). Methods: We evaluated the effect of activated endothelial cells on ovarian cancer cell proliferation and resistance to chemotherapy and investigated the survival pathways activated by endothelial co-culture. Results: The co-culture between OCCs and E4+ECs, induced an increase of OCCs proliferation both in vitro and in vivo. This co-culture induced an increase of Notch receptors expression on OCC surface and an increase of Jagged 1 expression on E4+ECs surface and activation of survival pathways leading to chemoresistance by E4+ECs. Conclusion: The targeting of aberrant NOTCH signaling could constitute a strategy to disrupt the pro-tumoral endothelial niche.

Original languageEnglish
Article number194
JournalJournal of translational medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 10 Jun 2019

Fingerprint

Ovarian Neoplasms
Endothelium
Tumors
Chemotherapy
Chemical activation
Endothelial cells
Cell proliferation
Coculture Techniques
Notch Receptors
Endothelial Cells
Cells
Cell Proliferation
Drug Therapy
Neoplasms
Tumor Microenvironment
Recurrence
Growth

Keywords

  • Cell-cell interactions
  • Endothelial cells
  • Ovarian cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Akt-activated endothelium promotes ovarian cancer proliferation through notch activation. / Hoarau, Jessica; Touboul, Cyril; Halabi, Najeeb; Blot-Dupin, Morgane; Lis, Raphael; Abi Khalil, Charbel; Rafii, Shahin; Tabrizi, Arash Rafii; Pasquier, Jennifer.

In: Journal of translational medicine, Vol. 17, No. 1, 194, 10.06.2019.

Research output: Contribution to journalArticle

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AU - Touboul, Cyril

AU - Halabi, Najeeb

AU - Blot-Dupin, Morgane

AU - Lis, Raphael

AU - Abi Khalil, Charbel

AU - Rafii, Shahin

AU - Tabrizi, Arash Rafii

AU - Pasquier, Jennifer

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AB - Background: One main challenge in ovarian cancer rests on the presence of a relapse and an important metastatic disease, despite extensive surgical debulking and chemotherapy. The difficulty in containing metastatic cancer is partly due to the heterotypic interaction of tumor and its microenvironment. In this context, evidence suggests that endothelial cells (EC) play an important role in ovarian tumor growth and chemoresistance. Here, we studied the role of tumor endothelium on ovarian cancer cells (OCCs). Methods: We evaluated the effect of activated endothelial cells on ovarian cancer cell proliferation and resistance to chemotherapy and investigated the survival pathways activated by endothelial co-culture. Results: The co-culture between OCCs and E4+ECs, induced an increase of OCCs proliferation both in vitro and in vivo. This co-culture induced an increase of Notch receptors expression on OCC surface and an increase of Jagged 1 expression on E4+ECs surface and activation of survival pathways leading to chemoresistance by E4+ECs. Conclusion: The targeting of aberrant NOTCH signaling could constitute a strategy to disrupt the pro-tumoral endothelial niche.

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