20
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      LIF mediates proinvasive activation of stromal fibroblasts in cancer.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Signaling crosstalk between tumor cells and fibroblasts confers proinvasive properties to the tumor microenvironment. Here, we identify leukemia inhibitory factor (LIF) as a tumor promoter that mediates proinvasive activation of stromal fibroblasts independent of alpha-smooth muscle actin (α-SMA) expression. We demonstrate that a pulse of transforming growth factor β (TGF-β) establishes stable proinvasive fibroblast activation by inducing LIF production in both fibroblasts and tumor cells. In fibroblasts, LIF mediates TGF-β-dependent actomyosin contractility and extracellular matrix remodeling, which results in collective carcinoma cell invasion in vitro and in vivo. Accordingly, carcinomas from multiple origins and melanomas display strong LIF upregulation, which correlates with dense collagen fiber organization, cancer cell collective invasion, and poor clinical outcome. Blockade of JAK activity by Ruxolitinib (JAK inhibitor) counteracts fibroblast-dependent carcinoma cell invasion in vitro and in vivo. These findings establish LIF as a proinvasive fibroblast producer independent of α-SMA and may open novel therapeutic perspectives for patients with aggressive primary tumors.

          Related collections

          Author and article information

          Journal
          Cell Rep
          Cell reports
          2211-1247
          Jun 12 2014
          : 7
          : 5
          Affiliations
          [1 ] INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Medical School, 28 Avenue Valombrose, F-06107 Nice, France.
          [2 ] Pathological Anatomy and Cytology Laboratory, 270 Avenue Sainte-Marguerite, F-06200 Nice, France.
          [3 ] Laboratory of Clinical and Experimental Pathology and Hospital-Integrated Tumor Biobank, Pasteur Hospital, F-06002 Nice, France.
          [4 ] INSERM, U1065, Mediterranean Centre for Molecular Medicine (C3M), University of Nice Sophia Antipolis, F-06204 Nice, France.
          [5 ] INSERM, U1081, CNRS, UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Medical School, 28 Avenue Valombrose, F-06107 Nice, France. Electronic address: gaggioli@unice.fr.
          Article
          S2211-1247(14)00338-6
          10.1016/j.celrep.2014.04.036
          24857661
          f91b67f5-71bf-4371-89a7-94b509032d7f
          Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
          History

          Comments

          Comment on this article