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Tumor exposed-lymphatic endothelial cells promote primary tumor growth via IL6.

Authors
  • Van de Velde, Maureen1
  • Ebroin, Marie1
  • Durré, Tania1
  • Joiret, Marc2
  • Gillot, Lionel1
  • Blacher, Silvia1
  • Geris, Liesbet2
  • Kridelka, Frédéric3
  • Noel, Agnès4
  • 1 Laboratory of Tumor and Development Biology, GIGA-Cancer, Liege University, B23, Avenue Hippocrate 13, Sart-Tilman, B-4000, Liege, Belgium. , (Belgium)
  • 2 Biomechanics Research Unit, GIGA-In Silico Medicine, Liege University, B34, Sart-Tilman, 4000, Liège, Belgium. , (Belgium)
  • 3 Laboratory of Tumor and Development Biology, GIGA-Cancer, Liege University, B23, Avenue Hippocrate 13, Sart-Tilman, B-4000, Liege, Belgium; Department of Obstetrics and Gynecology, CHU Liege, Sart-Tilman, 4000, Liege, Belgium. , (Belgium)
  • 4 Laboratory of Tumor and Development Biology, GIGA-Cancer, Liege University, B23, Avenue Hippocrate 13, Sart-Tilman, B-4000, Liege, Belgium. Electronic address: [email protected] , (Belgium)
Type
Published Article
Journal
Cancer letters
Publication Date
Jan 28, 2021
Volume
497
Pages
154–164
Identifiers
DOI: 10.1016/j.canlet.2020.10.020
PMID: 33080310
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Solid tumors are composed of tumor cells and stromal cells including lymphatic endothelial cells (LEC), which are mainly viewed as cells forming lymphatic vessels involved in the transport of metastatic and immune cells. We here reveal a new mechanism by which tumor exposed-LEC (teLEC) exert mitogenic effects on tumor cells. Our conclusions are supported by morphological and molecular changes induced in teLEC that in turn enhance cancer cell invasion in 3D cultures and tumor cell proliferation in vivo. The characterization of teLEC secretome by RNA-Sequencing and cytokine array revealed that interleukine-6 (IL6) is one of the most modulated molecules in teLEC, whose production was negligible in unexposed LEC. Notably, neutralizing anti-human IL6 antibody abrogated teLEC-mediated mitogenic effects in vivo, when LEC were mixed with tumor cells in the ear sponge assay. We here assign a novel function to teLEC that is beyond their role of lymphatic vessel formation. This work highlights a new paradigm, in which teLEC exert "fibroblast-like properties", contribute in a paracrine manner to the control of tumor cell properties and are worth considering as key stromal determinant in future studies. Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

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