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

Lionel W. Hebbard, Michèle Garlatti, Lawrence J T Young, Robert Cardiff, Robert G. Oshima, Barbara Ranscht

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1407-1416
Number of pages10
JournalCancer Research
Volume68
Issue number5
DOIs
StatePublished - Mar 1 2008

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this