Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis

Cancer Cell. 2008 Jan;13(1):23-35. doi: 10.1016/j.ccr.2007.12.004.

Abstract

Aberrant TGFbeta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis through a process involving metalloproteinase activity. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGF beta 1 in tumors with Tgfbr2 deletion. The recruitment of Gr-1+CD11b+ cells into tumors with Tgfbr2 deletion involves two chemokine receptor axes, the SDF-1/CXCR4 and CXCL5/CXCR2 axes. Together, these data indicate that Gr-1+CD11b+ cells contribute to TGFbeta-mediated metastasis through enhancing tumor cell invasion and metastasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • CD11b Antigen / metabolism*
  • Cell Line, Tumor
  • Female
  • Gene Deletion
  • Humans
  • Matrix Metalloproteinases / biosynthesis
  • Mice
  • Models, Biological
  • Myeloid Cells / enzymology
  • Myeloid Cells / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*

Substances

  • CD11b Antigen
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Matrix Metalloproteinases