Akt-activated endothelium promotes ovarian cancer proliferation through notch activation

Akt 激活的内皮细胞通过 Notch 激活促进卵巢癌增殖

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

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).

Conclusion

The targeting of aberrant NOTCH signaling could constitute a strategy to disrupt the pro-tumoral endothelial niche.

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.

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