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Cancers 2015, 7(3), 1658-1683; doi:10.3390/cancers7030856

The Role of Hedgehog Signaling in Tumor Induced Bone Disease

1
Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37235, USA
2
Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University, Nashville, TN 372335, USA
3
Department of Cancer Biology, Vanderbilt University, Nashville, TN 37235, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hui-Wen Lo
Received: 9 July 2015 / Revised: 13 August 2015 / Accepted: 18 August 2015 / Published: 26 August 2015
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Abstract

Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. View Full-Text
Keywords: Hedgehog signaling; Gli; cancer; bone; metastasis Hedgehog signaling; Gli; cancer; bone; metastasis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cannonier, S.A.; Sterling, J.A. The Role of Hedgehog Signaling in Tumor Induced Bone Disease. Cancers 2015, 7, 1658-1683.

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