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

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.

• Authors: Lionel W Hebbard, Michèle Garlatti, Lawrence J T Young, Robert D Cardiff, Robert G Oshima, Barbara Ranscht
• Journal: Cancer research (Cancer Res) Vol. 68 Issue 5 Pg. 1407-16 (Mar 01 2008) ISSN: 1538-7445 [Electronic] United States
• PMID: 18316604 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adiponectin
• Cadherins
• H-cadherin
• Platelet Endothelial Cell Adhesion Molecule-1

Topics

• Adiponectin (biosynthesis, metabolism)
• Animals
• Cadherins (metabolism, physiology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Male
• Mammary Neoplasms, Animal (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neoplasm Metastasis
• Neoplasm Transplantation
• Neovascularization, Pathologic
• Platelet Endothelial Cell Adhesion Molecule-1 (biosynthesis)