Acute hypoxia increases the aggressive characteristics and survival properties of prostate cancer cells

Ghafar, Mohamed A.; Anastasiadis, Aristotelis G.; Chen, Luyang; Burchardt, Martin; Olsson, Lars; Xie, Hui; Benson, Mitchell C.; Buttyan, Ralph

doi:10.1002/pros.10162

Cited by 91 publications

(73 citation statements)

References 27 publications

(28 reference statements)

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“…23,24 Studies have shown that there are significant associations between intratumoral hypoxia and tumor metastases, response to chemotherapy or radiotherapy and prognosis of cancer patients. [33][34][35][36][37] It has been shown that hypoxia modulates the expression of different sets of genes in cancer cells. 36 To generate gene therapy vectors that are effective for hypoxic tumor cells, it is crucial to use transcriptional control elements that are active in these cells.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35][36][37] It has been shown that hypoxia modulates the expression of different sets of genes in cancer cells. 36 To generate gene therapy vectors that are effective for hypoxic tumor cells, it is crucial to use transcriptional control elements that are active in these cells. The effect of hypoxia on the expression of the survivin gene was unknown.…”

Section: Discussionmentioning

confidence: 99%

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Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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Increasing evidence indicates that survivin, an inhibitor of apoptosis protein (IAP), is expressed in human cancer cells but is absent from most normal adult tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P) to direct therapeutic expression of a proapoptotic gene specifically in human tumor cells. First, we demonstrated that this promoter was highly active in human tumor cells but not in normal cells. Second, we found that Sur-P activity was upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's activity under hypoxia, we added a hypoxia-responsive element (HRE) from the vascular endothelial growth factor gene promoter in its 5 0 region, and showed that this combination resulted in a further increase in the level of gene expression in hypoxic tumor cells. Finally, we demonstrated that expression of an autocatalytic reverse caspase-3 gene by this promoter specifically induced apoptotic cell death in human tumor cells but not in normal cells. These findings support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel vectors for cancer gene therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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“…One specific HIF-2α target gene is Oct-4, which encodes a transcription factor essential for the pluripotency of stem cells. Its activation is responsible for tumor cell dedifferentiation that has been demonstrated in neuroblastomas, breast cancer, and is probably the same in other tumours [49][50][51] . Activation of the Notch signaling pathway also participates in the loss of cell differentiation 52,53 .…”

Section: Biological Functionsmentioning

confidence: 99%

Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1

Doktorova

Hraběta

Khalil

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. The aim of this review is to provide the information about molecular basis of hypoxia-induced chemoresistance, focusing on the possibility of diagnostic and therapeutic use. Results. Hypoxia is a common feature of tumors and represents an independent prognostic factor in many cancers. It is the result of imbalances in the intake and consumption of oxygen caused by abnormal vessels in the tumor and the rapid proliferation of cancer cells. Hypoxia-induced resistance to cisplatin, doxorubicin, etoposide, melphalan, 5-flouoruracil, gemcitabine, and docetaxel has been reported in a number of experiments. Adaptation of tumor cells to hypoxia has important biological effects. The most studied factor responsible for these effects is hypoxia-inducible factor-1 (HIF-1) that significantly contributes to the aggressiveness and chemoresistance of different tumors. The HIF-1 complex, induced by hypoxia, binds to target genes, thereby increasing the expression of many genes. In addition, the expression of hundreds of genes can be also decreased in response to hypoxia in HIF-1 dependent manner, but without the detection of HIF-1 in these genes' promoters. HIF-1 independent mechanisms for drug resistance in hypoxia have been described, however, they are still rarely reported. The first clinical studies focusing on diagnosis of hypoxia and on inhibition of hypoxia-induced changes in cancer cells are starting to yield results. Conclusions. The adaptation to hypoxia requires many genetic and biochemical responses that regulate one another. Hypoxia-induced resistance is a very complex field and we still know very little about it. Different approaches to circumvent hypoxia in tumors are under development.

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“…Colorectal cancer stem cells cultured at hypoxia show increased clonogenicity, inhibited differentiation and induced expression of markers associated with a stem cell-like phenotype (75). Also, prostate carcinoma LNCaP cells exposed to hypoxia downregulate differentiation-specific proteins such as prostatespecific antigen and androgen receptor, suggesting that dedifferentiation in response to hypoxia occurs also in prostate cancer (76).…”

Section: Hypoxia and Tumor Cell Differentiationmentioning

confidence: 99%

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Mohlin

Wigerup

Påhlman

2011

Seminars in Cancer Biology

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Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.Mohlin, Sofie; Wigerup, Caroline; Påhlman, Sven Link to publication Citation for published version (APA): Mohlin, S., Wigerup, C., & Påhlman, S. (2011). Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Seminars in Cancer Biology, 21(4), 276-282. DOI: 10.1016276-282. DOI: 10. /j.semcancer.2011 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Neural crest and development of the sympathetic nervous systemThe sympathetic nervous system (SNS) originates from the neural crest, an ephemeral structure during vertebrate development. Located along the neural fold, cells on the neural tube in the ectoderm give rise to the neural crest, in turn generating different derivatives, such as the cranial, hindbrain, vagal and trunk neural crest (reviewed in (9)). Trunk neural crest cells migrate from the neural tube along two defined routes, with one group of cells migrating early along a ventral pathway, giving rise to glial cells and neurons, whereas a later migrating group of cells follows a lateral pathway and gives rise to melanocytes in the skin (10, 11). These mutations were rare in all four studies indicating locus heterogeneity for predisposition of inherited disease, but still demonstrated the importance of the PHOX2B gene in neuroblastoma oncogenesis and initiation (Fig. 1) (58), and Fig. 1). Neuroblastoma differentiation stage and clinical outcomeThere is a well-documented difference in aggressive behavior between the morphologically undifferentiated (neuroblastoma proper) and the differentiated (ganglioneuroblastoma, Cellular adaptation to hypoxiaThe biological consequences of hypoxia involve induced angiogenesis, a switch in glucose metabolism and increased invasion and migration capacities, changes that stimulate tumor progression. The hypoxic response is mainly mediated by stabilization of the hypoxia inducible factor (HIF) proteins. HIFs are heterodimeric transcription factors composed of an oxygen sensitive  subunit and a constitutively expressed  subunit. At physiological oxygen levels, the  subunit is hydroxylated by the oxygen-dependent prolyl hydroxylases (PHDs), leading to interaction with the von Hippel Lindau-ubiquitin ligase complex, followed by ubiquitination and proteasomal degradation. At hypoxia, the PHDs are inactive leading to the 9 stabilization of the HIF- subunits, and by dimerization with the  subunit the comple...

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Acute hypoxia increases the aggressive characteristics and survival properties of prostate cancer cells

Abstract: This study demonstrates that even acute hypoxia has the potential to drastically alter the growth, differentiation characteristics, and apoptotic sensitivity of a prostate cancer cell.

Cited by 91 publications

References 27 publications

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

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