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

Int J Cancer. 2019 Oct 1;145(7):1913-1920. doi: 10.1002/ijc.32286. Epub 2019 Apr 9.

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.

Keywords: colorectal cancer; extracellular matrix; gene expression profile; lymphatic endothelium; matrisome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Bone Morphogenetic Proteins
  • GDF11 protein, human
  • Growth Differentiation Factors