Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11

Federica Ungaro, Piergiuseppe Colombo, Luca Massimino, Giovanni Stefano Ugolini, Carmen Correale, Marco Rasponi, Valentina Garlatti, Federica Rubbino, Carlotta Tacconi, Paola Spaggiari, Antonino Spinelli, Michele Carvello, Matteo Sacchi, Salvatore Spanò, Stefania Vetrano, Alberto Malesci, Laurent Peyrin-Biroulet, Silvio Danese, Silvia D'Alessio

Research output: Contribution to journalArticle

Abstract

Colorectal cancer (CRC) is one of the most malignant tumors worldwide. Stromal cells residing in the tumor microenvironment strongly contribute to cancer progression through their crosstalk with cancer cells and extracellular matrix. Here we provide the first evidence that CRC-associated lymphatic endothelium displays a distinct matrisome-associated transcriptomic signature, which distinguishes them from healthy intestinal lymphatics. We also demonstrate that CRC-associated human intestinal lymphatic endothelial cells regulate tumor cell growth via growth differentiation factor 11, a soluble matrisome component which in CRC patients was found to be associated with tumor progression. Our data provide new insights into lymphatic contribution to CRC growth, aside from their conventional role as conduits of metastasis.

Original languageEnglish
Pages (from-to)1913-1920
Number of pages8
JournalInternational Journal of Cancer
Volume145
Issue number7
DOIs
Publication statusPublished - Oct 1 2019

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Keywords

  • Animals
  • Bone Morphogenetic Proteins/genetics
  • Caco-2 Cells
  • Cell Culture Techniques/methods
  • Cell Proliferation
  • Cells, Cultured
  • Colorectal Neoplasms/genetics
  • Disease Progression
  • Endothelial Cells/chemistry
  • Endothelium, Lymphatic/chemistry
  • Extracellular Matrix/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Growth Differentiation Factors/genetics
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Tumor Microenvironment

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