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.
Hebbard
Lionel W
LW
Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Garlatti
Michèle
M
Young
Lawrence J T
LJ
Cardiff
Robert D
RD
Oshima
Robert G
RG
Ranscht
Barbara
B
D052242:Adiponectin / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis
D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin; D019408:Platelet Endothelial Cell Adhesion Molecule-1