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T-cadherin supports angiogenesis and adiponectin association with the vasculature in a mouse mammary tumor model.

T-cadherin delineates endothelial, myoepithelial, and ductal epithelial cells in the normal mouse mammary gland, and becomes progressively restricted to the vasculature during mammary tumorigenesis. To test the function of T-cadherin in breast cancer, we inactivated the T-cadherin (Cdh13) gene in mice and evaluated tumor development and pathology after crossing the mutation into the mouse mammary tumor virus (MMTV)-polyoma virus middle T (PyV-mT) transgenic model. We report that T-cadherin deficiency limits mammary tumor vascularization and reduces tumor growth. Tumor transplantation experiments confirm the stromal role of T-cadherin in tumorigenesis. In comparison with wild-type MMTV-PyV-mT controls, T-cadherin-deficient tumors are pathologically advanced and metastasize to the lungs. T-cadherin is a suggested binding partner for high molecular weight forms of the circulating, fat-secreted hormone adiponectin. We discern adiponectin in association with the T-cadherin-positive vasculature in the normal and malignant mammary glands and report that this interaction is lost in the T-cadherin null condition. This work establishes a role for T-cadherin in promoting tumor angiogenesis and raises the possibility that vascular T-cadherin-adiponectin association may contribute to the molecular cross-talk between tumor cells and the stromal compartment in breast cancer.

Pubmed ID: 18316604

Authors

  • Hebbard LW
  • Garlatti M
  • Young LJ
  • Cardiff RD
  • Oshima RG
  • Ranscht B

Journal

Cancer research

Publication Data

March 1, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 098778
  • Agency: NCI NIH HHS, Id: CA089140
  • Agency: NICHD NIH HHS, Id: HD25938
  • Agency: NICHD NIH HHS, Id: P01 HD025938
  • Agency: NICHD NIH HHS, Id: P01 HD025938-16A29003
  • Agency: NICHD NIH HHS, Id: P01 HD025938-179003
  • Agency: NCI NIH HHS, Id: U01 CA105490-01

Mesh Terms

  • Adiponectin
  • Animals
  • Antigens, CD31
  • Cadherins
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Male
  • Mammary Neoplasms, Animal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neovascularization, Pathologic