Bone morphogenetic protein 4 is induced in hepatocellular carcinoma by hypoxia and promotes tumor progression

Maegdefrau, Ulrike; Amann, Thomas; Winklmeier, Andreas; Braig, Simone; Schubert, Tobias; Weiß, TS; Schardt, K; Warnecke, Christina; Bosserhoff, A. K.; Hellerbrand, Claus

doi:10.1055/s-0029-1191882

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“…Connective tissue growth factor (Higgins et al 2004 ) is involved in osteoclastogenesis and bone resorption, liberating tumorpromoting factors from the bone matrix (Kang et al 2003 ;Nozawa et al 2009 ). These tumor-promoting factors include bone morphogenic proteins and transforming growth factor-β, which also are upregulated by hypoxia signaling (Falanga et al 1991 ;Maegdefrau et al 2009 ). Hypoxia-induced osteopontin interacts with osteoclasts that express αvβ3, thus promoting bone metastasis (Engleman et al 1997 ).…”

Section: Hypoxia and The Selection Of Metastatic Sitesmentioning

confidence: 99%

Hypoxia-Mediated Metastasis

Chang

Erler

2013

Advances in Experimental Medicine and Biology

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Metastasis is responsible for more than 90 % of deaths among cancer patient. It is a highly complex process that involves the interplay between cancer cells, the tumor microenvironment, and even noncancerous host cells. Metastasis can be seen as a step-wise process: acquisition of malignant phenotype, invasion into surrounding tissue, intravasation into blood vessels, survival in circulation, extravasation to distant sites, and colonization of new organs. Before the actual metastatic process, the secondary site is also prepared for the arrival of the cancer cells through formation of "premetastatic niches." Hypoxia (low oxygen tension) is commonly found in solid tumors more than a few millimeters cubed and often is associated with a poor prognosis. Hypoxia increases angiogenesis, cancer cell survival, and metastasis. This chapter described how hypoxia regulates each step of the metastatic process and how blocking hypoxia-driven metastasis through targeting hypoxia-inducible factor 1, or downstream effector molecules such as the lysyl oxidase family may represent highly effective preventive strategies against metastasis in cancer patients.

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