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STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

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Author

  • Cristina Pena
  • Maria Virtudes Cespedes
  • Maja Bradic Lindh
  • Sara Kiflemariam
  • Artur Mezheyeuski
  • Per-Henrik Edqvist
  • Christina Hagglof
  • Helgi Birgisson
  • Linda Bojmar
  • Karin Jirström
  • Per Sandstrom
  • Eleonor Olsson
  • Srinivas Veerla
  • Alberto Gallardo
  • Tobias Sjoblom
  • Andy C. -M. Chang
  • Roger R. Reddel
  • Ramon Mangues
  • Martin Augsten
  • Arne Ostman
Show all

Summary, in English

Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis. Cancer Res; 73(4); 1287-97. (C) 2012 AACR.

Department/s

Publishing year

2013

Language

English

Pages

1287-1297

Publication/Series

Cancer Research

Volume

74

Issue

4

Document type

Journal article

Publisher

American Association for Cancer Research Inc.

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1538-7445