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

Hebbard, Lionel W., Garlatti, Michèle, Young, Lawrence J.T., Cardiff, Robert D., Oshima, Robert G., and Ranscht, Barbara (2008) T-cadherin supports angiogenesis and adiponectin association with the vasculature in a mouse mammary tumor model. Cancer research, 68 (5). pp. 1407-1416.

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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.

Item ID: 40171
Item Type: Article (Research - C1)
ISSN: 1538-7445
Funders: National Institute of Health (NIH), Department of Defense (DOD), National Cancer Institute (NCI), 2005 Fishman Award
Projects and Grants: NIH grant HD25938, DOD grant W81-XWH-04-1-0574, NCI grant CA 098778, NCI grant CA089140, NCI grant U01 CA105490-01, DOD grant DAMD17-02-1-0694
Date Deposited: 31 Aug 2015 01:44
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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