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

Journal Publication ResearchOnline@JCU
Hebbard, Lionel W.;Garlatti, Michèle;Young, Lawrence J.T.;Cardiff, Robert D.;Oshima, Robert G.;Ranscht, Barbara
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.

Journal

Cancer Research

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Volume

68

ISBN/ISSN

1538-7445

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Issue

5

Pages Count

10

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Publisher

American Association for Cancer Research

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Date

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EISSN

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DOI

10.1158/0008-5472.CAN-07-2953