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Angiogenesis and Bone Metastasis: Implications for Diagnosis, Prevention and Treatment

Part of the Cancer Metastasis – Biology and Treatment book series (CMBT, volume 12)

Abstract

Angiogenesis consists of the mechanism by which new blood vessels are formed within the tumor to sustain its development and growth. This “angiogenic switch” is mediated by various molecules deriving from the cancer cell and/or the tumor-associated stroma and is promoted either by oncogene activation or by the physiological response of any cell to the hypoxic stress. The angiogenic switch is governed by the balance between angiogenic inducers and inhibitors.

There is a certain affinity between tumors sites and metastatic sites; that is the theory of “seed and soil”: certain tumor cells (the “seed”) have a specific affinity for the milieu of certain organs (the “soil”). Metastases result only when the seed and soil are compatible. The pathophysiology of bone metastasis is complex, involving different cell populations and regulatory proteins. The traditional idea that bone metastases are either osteoblastic or osteolytic represents in fact a continuum.

There is a multiplicity of reasons for a tumors’ propensity to metastasize to bone: Increased blood flow in red marrow and the presence of adhesive molecules on tumor cells are the most important. Adhesion triggers the secretion of angiogenic factors and bone resorbing factors from tumor cells that enable cancer cell survival and growth. The unique bone environment characterized by the continuous remodelling through osteoclast and osteoblast activity on trabecular surfaces provides cancer cells a soil rich in growth factors, such as transforming growth factor ––β(TGF-β), fibroblast growth factor (FGF), platelet- derived growth factor (PDGF)), and insulin growth factors (IGFs). Physical factors within the bone microenvironment, including low oxygen levels, acidic pH, and high extracellular calcium concentrations, may also enhance tumor growth. Bone-derived chemokines such as osteopontin, bone sialoprotein, and stromal-derived factor also act as chemoattractants for cancer cells.

Therefore, the most important angiogenic molecules in bone metastasis are VEGF, heparenase, TGF-β, IGF, PDGF, Interleukin- 8 (IL-8) and IL-6. Angiogenesis opens up a whole era of new treatment modalities for bone metastases: biphosphonates can act as anti-angiogenic agents and a field of targeted anti-angiogenic therapies for bone metastases is also emerging.

Keywords

Angiogenesis Angiogenic factors Bone metastasis Cancer Therapy 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Radiation Oncology DepartmentDemocritus University of Thrace, Medical SchoolDragana 68 100Greece

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