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Bone Structural Components Regulating Sites of Tumor Metastasis

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Abstract

Tumors such as breast, lung, and prostate frequently metastasize to bone, where they can cause intractable pain and increase the risk of fracture in patients. When tumor cells metastasize to bone, they interact with the microenvironment to promote bone destruction primarily through the secretion of osteolytic factors by the tumor cells and the subsequent release of growth factors from the bone. Our recent data suggest that the differential rigidity of the mineralized bone microenvironment relative to that of soft tissue regulates the expression of osteolytic factors by the tumor cells. The concept that matrix rigidity regulates tumor growth is well established in solid breast tumors, where increased rigidity stimulates tumor cell invasion and metastasis. Our studies have indicated that a transforming growth factor-β (TGF-β) and Rho-associated kinase (ROCK)–dependent mechanism is involved in the response of metastatic tumor cells to the rigid mineralized bone matrix. In this review, we will discuss the interactions between ROCK and TGF-β signaling, as well as potential new therapies that target these pathways.

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Acknowledgment

The authors acknowledge financial support from the National Institutes of Health Breast Cancer SPORE (P50 CA098131), P01 CA040035, and Tumor Microenvironment Network (TMEN) (U54 CA126505) grants.

Disclosure

Conflicts of interest: J.A. Sterling: none; S.A. Guelcher: has been a consultant and has received funding for his laboratory from Osteotech, Inc.

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Authors and Affiliations

  1. Department of Veterans Affairs: Tennessee Valley Healthcare System (VISN 9), Nashville, TN, USA

    Julie A. Sterling

  2. Department of Cancer Biology, Vanderbilt University Medical Center, 1235 MRB IV, 2222 Pierce Avenue 37232, Nashville, TN, 37235, USA

    Julie A. Sterling

  3. Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA

    Julie A. Sterling & Scott A. Guelcher

  4. Department of Chemical and Biomolecular Engineering, Vanderbilt University, 2400 Highland Avenue, 107 Olin Hall, Nashville, TN, 37235–1604, USA

    Scott A. Guelcher

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  1. Julie A. Sterling
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Correspondence to Scott A. Guelcher.

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Sterling, J.A., Guelcher, S.A. Bone Structural Components Regulating Sites of Tumor Metastasis. Curr Osteoporos Rep 9, 89–95 (2011). https://doi.org/10.1007/s11914-011-0052-5

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