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generates selection pressure for the development of therapy tolerant aggressive
tumor consisting of CSC phenotypes (Lin and Yun 2010 ). Moreover, hypoxia plays
a crucial role in maintaining CSCs in their undifferentiated state and permits the
accumulation of genetic and epigenetic insults over an extended period of time and
aids in self-renewal. HIFs are reported to target genes like Wnt, cMyc, Notch, Oct4
which are involved in maintaining stem properties (Fig. 11.3) (Keith and Simon
2007 ; Winquist et al. 2009 ; Qing and Simon 2009 ). Recent reports advocate that
hypoxic microenvironment may promote the stem-like biological properties of
laryngeal cancer cell lines by the intensification of the CD133+ stem cell
Fig. 11.3 Crosstalk between cancer stem cells and microenvironment. Tumor associated cells
including fibroblast, macrophages, T cells, B cells, neutrophills and endothelial cells secretes of
growth factors, interleukin and chemokines that helps in proliferation, angiogenesis and immune
evasion. CSCs encourage the proliferation of tumor associated cells by secreting secrete growth
factors and chemokines. Hypoxia in the tumor microenvironment induces the production of
HIF-1α, Oct4, Wnt and Notch and endorses stem like-features in cancer cells
P.P. Naik et al.