Hypoxia and cancer

Abstract

A major feature of solid tumours is hypoxia, decreased availability of oxygen, which increases patient treatment resistance and favours tumour progression. How hypoxic conditions are generated in tumour tissues and how cells respond to hypoxia are essential questions in understanding tumour progression and metastasis. Massive tumour-cell proliferation distances cells from the vasculature, leading to a deficiency in the local environment of blood carrying oxygen and nutrients. Such hypoxic conditions induce a molecular response, in both normal and neoplastic cells, that drives the activation of a key transcription factor; the hypoxia-inducible factor. This transcription factor regulates a large panel of genes that are exploited by tumour cells for survival, resistance to treatment and escape from a nutrient-deprived environment. Although now recognized as a major contributor to cancer progression and to treatment failure, the precise role of hypoxia signalling in cancer and in prognosis still needs to be further defined. It is hoped that a better understanding of the mechanisms implicated will lead to alternative and more efficient therapeutic approaches.

Hypoxia-inducible factor (HIF)-1α suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction

“…[16][17][18]22 HIF-1a is overexpressed in many tumors 22,23 including some hematological malignancies such as MM. [27][28][29]35 We and others 27,35 have recently shown that BM microenvironment is hypoxic both in MM patients 27 and in mice.…”

“…It is critical to the regulation of the angiogenic switch in those cancers, by regulating the production of the pro-angiogenic molecules. [16][17][18] Tumor adaptation to hypoxia is mainly due to the hypoxia-inducible factor (HIF)-1, a key transcription factor that regulates pro-angiogenic factors, angiogenesis and tumor progression in solid tumors. [19][20][21][22][23] HIF-1 is a heterodimeric DNA binding complex highly inducible by hypoxia and is composed of two basic helix-loop-helix proteins, including the constitutive HIF-1b subunit and the hypoxiainducible a-subunit.…”

Angiogenesis and Multiple Myeloma

“…It has also been reported that there is no significant difference in the reduced BM pO 2 and sO 2 in MM patients as compared with MGUS patients [112]. However, in a MM mouse model it has been reported that both normal and MM-infiltrated BM are hypoxic, although the level of oxygen was lower in MM BM [104]. This discrepancy could be due either to the different method used in the detection of hypoxia or to the lower physiological oxygen tension reported in mice as compared to human [112][113][114].…”

“…Hypoxia is a common feature of solid tumors that is associated with angiogenesis and the malignant phenotype and is critical in the regulation of the angiogenic switch [104,105]. Tumor adaptation to hypoxia is mainly due to the hypoxia-inducible factor (HIF)-1, a key transcription factor that regulates angiogenesis and tumor progression in solid cancers [106][107][108][109][110][111].…”

Expression of Hypoxia-inducible Factor Prolyl Hydroxylase 3 HIFPH3 in Human Non-small Cell Lung Cancer (NSCLC) and Its Correlation with Prognosis

“…This is called Warburg effect (Samudio et al, 2009). The adaption of cancer cells to hypoxia is not only essential for tumor growth and development (Pouysségur et al, 2006), but also accounts for radio-and chemo-therapy tolerance (Brown, 2002;Brahimi-Horn et al, 2007;Vaupel, 2008).…”