![]() ![]() Significant evidence exists to indicate that migration of tumor cells during hematogenous metastasis is accelerated by a HIF-driven response ( Liao et al., 2007 Lu et al., 2010 Zhong et al., 1999). The role of the tumor cell in metastasis has been widely examined and discussed ( Chambers et al., 2002 Gupta and Massagué, 2006). ![]() Hypoxic response via HIF activation also includes expression of factors such as vascular endothelial growth factor ( VEGF), and inducible nitric oxide synthase ( iNOS) that are known to facilitate both angiogenesis and tumor cell access to the circulatory system ( Ambs et al., 1998 Claffey et al., 1996 Shweiki et al., 1992 Ziche and Morbidelli, 2009). Hypoxia itself triggers the induction of the hypoxia inducible (HIF) transcription factors these in turn are linked to changes in the capacity of tumor cells to migrate, undergo epithelial to mesenchymal transition, and to a number of other processes intrinsic to metastasis ( Chen et al., 2010 Haase, 2009 Liao et al., 2007 Yang et al., 2008). There is a link between the metastatic process and oxygen deprivation ( Brizel et al., 1996 Rofstad et al., 2010 Voss et al., 2011).
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