Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis Through Elevated SDF-1/CXCL12 Secretion

Cell. 2005 May 6;121(3):335-48. doi: 10.1016/j.cell.2005.02.034.

Abstract

Fibroblasts often constitute the majority of the stromal cells within a breast carcinoma, yet the functional contributions of these cells to tumorigenesis are poorly understood. Using a coimplantation tumor xenograft model, we demonstrate that carcinoma-associated fibroblasts (CAFs) extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammary fibroblasts derived from the same patients. The CAFs, which exhibit the traits of myofibroblasts, play a central role in promoting the growth of tumor cells through their ability to secrete stromal cell-derived factor 1 (SDF-1); CAFs promote angiogenesis by recruiting endothelial progenitor cells (EPCs) into carcinomas, an effect mediated in part by SDF-1. CAF-secreted SDF-1 also stimulates tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells. Our findings indicate that fibroblasts within invasive breast carcinomas contribute to tumor promotion in large part through the secretion of SDF-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology*
  • Cell Communication
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Cell Separation
  • Chemokine CXCL12
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Chemotaxis / physiology
  • Endothelial Cells / pathology
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / transplantation
  • Gene Expression / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Models, Biological
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Paracrine Communication / physiology
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / genetics
  • Stem Cells / pathology
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Stromal Cells / transplantation
  • Xenograft Model Antitumor Assays

Substances

  • Actins
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Receptors, CXCR4