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Integrin αvβ3 Signaling in Tumor-Induced Bone Disease

by Kristin A. Kwakwa 1,2,3 and Julie A. Sterling 1,2,3,4,5,*
1
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA
2
Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
3
Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA
4
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA
5
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
*
Author to whom correspondence should be addressed.
Cancers 2017, 9(7), 84; https://doi.org/10.3390/cancers9070084
Received: 15 June 2017 / Revised: 5 July 2017 / Accepted: 5 July 2017 / Published: 8 July 2017
(This article belongs to the Special Issue Integrins in Cancer)
Tumor-induced bone disease is common among patients with advanced solid cancers, especially those with breast, prostate, and lung malignancies. The tendency of these cancers to metastasize to bone and induce bone destruction is, in part, due to alterations in integrin expression and signaling. Substantial evidence from preclinical studies shows that increased expression of integrin αvβ3 in tumor cells promotes the metastatic and bone-invasive phenotype. Integrin αvβ3 mediates cell adhesion to several extracellular matrix proteins in the bone microenvironment which is necessary for tumor cell colonization as well as the transmission of mechanical signals for tumor progression. This review will discuss the αvβ3 integrin receptor in the context of tumor-induced bone disease. Specifically, the focus will be the role of αvβ3 in modulating cancer metastasis to bone and tumor cell response to the bone microenvironment, including downstream signaling pathways that contribute to tumor-induced osteolysis. A better understanding of integrin dysregulation in cancer is critical to developing new therapeutics for the prevention and treatment of bone metastases. View Full-Text
Keywords: integrins; bone tumors; bone metastasis; tumor microenvironment integrins; bone tumors; bone metastasis; tumor microenvironment
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Kwakwa, K.A.; Sterling, J.A. Integrin αvβ3 Signaling in Tumor-Induced Bone Disease. Cancers 2017, 9, 84.

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