Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Coordinating Effect of VEGFC and Oleic Acid Drives Tumor Lymphangiogenesis

Florent Morfoisse
ORCID logo ,
Fabienne De Toni
,
Jeremy Nigri
,
Mohsen Hosseini
,
Audrey Zamora
,
Florence Tatin
,
Francoise Pujol
,
Jean-Emmanuel Sarry
,
Dominique Langin
,
Eric Lacazette
ORCID logo ,
Anne-Catherine Prats
ORCID logo ,
Richard Tomasini
ORCID logo ,
Jean Galitzky
,
Anne Bouloumié
,
Barbara Garmy-Susini
* ORCID logo
Version 1 : Received: 7 April 2021 / Approved: 8 April 2021 / Online: 8 April 2021 (10:11:23 CEST)

A peer-reviewed article of this Preprint also exists.

Morfoisse, F.; De Toni, F.; Nigri, J.; Hosseini, M.; Zamora, A.; Tatin, F.; Pujol, F.; Sarry, J.-E.; Langin, D.; Lacazette, E.; Prats, A.-C.; Tomasini, R.; Galitzky, J.; Bouloumié, A.; Garmy-Susini, B. Coordinating Effect of VEGFC and Oleic Acid Participates to Tumor Lymphangiogenesis. Cancers 2021, 13, 2851. Morfoisse, F.; De Toni, F.; Nigri, J.; Hosseini, M.; Zamora, A.; Tatin, F.; Pujol, F.; Sarry, J.-E.; Langin, D.; Lacazette, E.; Prats, A.-C.; Tomasini, R.; Galitzky, J.; Bouloumié, A.; Garmy-Susini, B. Coordinating Effect of VEGFC and Oleic Acid Participates to Tumor Lymphangiogenesis. Cancers 2021, 13, 2851.

Abstract

In cancer, the lymphatic system is hijacked by tumor cells to escape from primary tumor and to metastasize to the sentinel lymph nodes. Tumor lymphangiogenesis is stimulated by the vascular endothelial growth factors-C (VEGFC) after binding to its receptor VEGFR-3. However, how VEGFC cooperates with other molecules to promote lymphatic neovessels growth is not fully determined. Here, we found that tumor lymphangiogenesis developed in tumoral lesions and in their surrounding adipose tissue (AT). Interestingly, lymphatic vessel density correlated with an increase of circulating free fatty acids (FFA) in the lymph from tumor-bearing mice. We found that adipocyte-released FFA are uploaded by lymphatic endothelial cells (LEC) to stimulate their sprouting. Lipidomic analysis identified the monounsaturated oleic acid (OA) as the major circulating FFA in the lymph in tumoral context. OA transporters FATP-3, -6 and CD36 were only upregulated on LEC in the presence of VEGFC showing a collaborative effect of these molecules. OA released from adipocytes is taken up by LECs to stimulate the fatty acid β-oxidation, leading to increase adipose tissue lymphangiogenesis. Our results provide new insights on the dialogue between tumors and adipocytes via the lymphatic system and identify a key role for adipocyte-derived FFA in the promotion of lymphangiogenesis, revealing novel therapeutic opportunities for inhibitors of lymphangiogenesis in cancer.

Keywords

lymphangiogenesis; free fatty acids; vegfc

Subject

Biology and Life Sciences, Anatomy and Physiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.