The role of hypoxia-inducible factors in tumorigenesis

Rankin, Erinn B.; Giaccia, Amato J.

doi:10.1038/cdd.2008.21

Cited by 719 publications

(706 citation statements)

References 95 publications

(90 reference statements)

Supporting

Mentioning

676

Contrasting

Unclassified

Order By: Relevance

“…[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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2013

View full text Add to dashboard Cite

Hypoxia-inducible transcription factor-1 (HIF-1a) is overexpressed in multiple myeloma (MM) cells within the hypoxic microenvironment. Herein, we explored the effect of persistent HIF-1a inhibition by a lentivirus short hairpin RNA pool on MM cell growth either in vitro or in vivo and on the transcriptional and pro-angiogenic profiles of MM cells. HIF-1a suppression did not have a significant impact on MM cell proliferation and survival in vitro although, increased the antiproliferative effect of lenalidomide. On the other hand, we found that HIF-1a inhibition in MM cells downregulates the pro-angiogenic genes VEGF, IL8, IL10, CCL2, CCL5 and MMP9. Pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1a. The effect of HIF-1a inhibition was assessed in vivo in nonobese diabetic/severe combined immunodeficiency mice both in a subcutaneous and an intratibial MM model. HIF-1a inhibition caused a dramatic reduction in the weight and volume of the tumor burden in both mouse models. Moreover, a significant reduction of the number of vessels and vascular endothelial growth factors (VEGFs) immunostaining was observed. Finally, in the intratibial experiments, HIF-1a inhibition significantly blocked bone destruction. Overall, our data indicate that HIF-1a suppression in MM cells significantly blocks MM-induced angiogenesis and reduces MM tumor burden and bone destruction in vivo, supporting HIF-1a as a potential therapeutic target in MM.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…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]. HIF-1 is a heterodimeric DNA binding complex composed of two basic helix-loop-helix proteins, including the constitutively expressed HIF-1β and the hypoxia-inducible α-subunit HIF-1α [106][107][108][109].…”

Section: Hypoxia and Hypoxia-inducible Factor-1 In Myeloma-induced Anmentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

View full text Add to dashboard Cite

The bone marrow microenvironment in multiple myeloma is characterized by an increased microvessel density. The production of pro-angiogenic molecules is increased and the production of angiogenic inhibitors is suppressed, leading to an "angiogenic switch". Here we present an overview of the role of angiogenesis in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the microenvironment, and the mechanisms involved in the myeloma-induced angiogenic switch. Current data suggest that the increased bone marrow angiogenesis in multiple myeloma is due to the aberrant expression of angiogenic factors by myeloma cells, the subsequent increase in pro-angiogenic activity of normal plasma cells as a result of myeloma cell angiogenic activity, and the increased number of plasma cells overall. Hypoxia also contributes to the angiogenic properties of the myeloma marrow microenvironment. The transcription factor hypoxia-inducible factor-1α is overexpressed by myeloma cells and affects their transcriptional and angiogenic profiles. In addition, potential roles of the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7 have also been recently highlighted as repressors of angiogenesis and pro-angiogenic related genes, respectively. This complex pathogenetic model of myeloma-induced angiogenesis suggests that several proangiogenic molecules and related genes in myeloma cells and the microenvironment are potential therapeutic targets.

show abstract

“…Hypoxia upregulates hypoxia induced factor 1α (HIF‐1α)3 and collagen,4 which builds up a dense extracellular matrix (ECM) and severely limits drug delivery efficiency and antitumor efficacy 5. Moreover, tumor cells under hypoxic condition are often caught in an inactive state and are insensitive to chemotherapeutic agents 6.…”

Section: Introductionmentioning

confidence: 99%

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Zhu

Huang

et al. 2018

Advanced Science

View full text Add to dashboard Cite

Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX‐loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.

show abstract

The role of hypoxia-inducible factors in tumorigenesis

Cited by 719 publications

References 95 publications

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

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

Angiogenesis and Multiple Myeloma

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Contact Info

Product

Resources

About