The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans

Proc Natl Acad Sci U S A. 2007 May 1;104(18):7570-5. doi: 10.1073/pnas.0702095104. Epub 2007 Apr 24.


A better understanding of tumor metastasis requires development of animal models that authentically reproduce the metastatic process. By modifying an existing mouse model of breast cancer, we discovered that macrophage-stimulating protein promoted breast tumor growth and metastasis to several organs. A special feature of our findings was the occurrence of osteolytic bone metastases, which are prominent in human breast cancer. To explore the clinical relevance of our model, we examined expression levels of three genes involved in activation of the MSP signaling pathway (MSP, MT-SP1, and MST1R) in human breast tumors. We found that overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of both metastasis and death in human breast cancer patients and significantly increased the accuracy of an existing gene expression signature for poor prognosis. These data suggest that signaling initiated by MSP is an important contributor to metastasis of breast cancer and introduce an independent biomarker for assessing the prognosis of humans with breast cancer.

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.

MeSH terms

  • Animals
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Transformation, Neoplastic / pathology
  • Disease Models, Animal*
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology*
  • Mice
  • Neoplasm Metastasis*
  • Prognosis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Risk Factors
  • Serine Endopeptidases / metabolism
  • Signal Transduction*
  • Time Factors


  • Proto-Oncogene Proteins
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • RON protein
  • Receptor Protein-Tyrosine Kinases
  • Serine Endopeptidases
  • ST14 protein, human