Tumor hypoxia in pelvic recurrences of cervical cancer

Höckel, Michael; Schlenger, Karlheinz; Höckel, Susanne; Aral, Billur; Schäffer, U.; Vaupel, Peter

doi:10.1002/(sici)1097-0215(19980821)79:4<365::aid-ijc10>3.0.co;2-4

Cited by 163 publications

(82 citation statements)

References 17 publications

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“…Thus, microenvironmental control of chemokine receptor expression will track an individual cell along an appropriate gradient. Hypoxia is an important factor in solid tumours; it can be an important prognostic indicator in gynaecological cancer (Hockel et al, 1998) and has been shown to regulate the expression of the chemokines CCL2 (Negus et al, 1998) and CXCL8 (IL-8) (Xu et al, 1999) and the chemokine receptor CXCR1 (Grutkoski et al, 1999). Moreover, it is being exploited as a therapeutic strategy in tumours (Griffiths et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

Scotton¹,

Milliken

Wilson³

et al. 2001

Br J Cancer

100

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SummaryTo understand the chemokine network in a tissue, both chemokine and chemokine receptor expression should be studied. Human epithelial ovarian tumours express a range of chemokines but little is known about the expression and localisation of chemokine receptors. With the aim of understanding chemokine action in this cancer, we investigated receptors for CC-chemokines and their ligands in 25 biopsies of human ovarian cancer. CC-chemokine receptor mRNA was generally absent from solid tumours, the exception being CCR1 which was detected in samples from 75% of patients. CCR1 mRNA localised to macrophages and lymphocytes and there was a correlation between numbers of CD8 + and CCR1 expressing cells (P = 0.031). mRNA for 6 CC-chemokines was expressed in a majority of tumour samples. In a monocytic cell line in vitro, we found that CCR1 mRNA expression was increased 5-fold by hypoxia. We suggest that the CC-chemokine network in ovarian cancer is controlled at the level of CC-chemokine receptors and this may account for the phenotypes of infiltrating cells found in these tumours. The leukocyte infiltrate may contribute to tumour growth and spread by providing growth survival factors and matrix metalloproteases. Thus, CCR1 may be a novel therapeutic target in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

Scotton¹,

Milliken

Wilson³

et al. 2001

Br J Cancer

100

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“…However, it is apparent that upregulation of HIF-1 transactivates antiproliferative and proapoptotic genes (Bacon and Harris, 2004). Regions of hypoxia are known to exist within many solid tumours and the extent of tumour hypoxia is regarded as an important prognostic factor influencing neoplastic aggression, resistance to therapy and overall patient survival (Hockel et al, 1998;Stadler et al, 1999;Knowles and Harris, 2001;Harris, 2002). This suggests that antitumorigenic proteins that are hypoxically upregulated are either non-functional or the tumour escapes from negative signalling.…”

Section: Introductionmentioning

confidence: 99%

Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer

et al. 2006

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Hypoxia, via the hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2), upregulates many genes involved in cell survival. However, proapoptotic pathways are also induced. BCL-2/adenovirus E1B-19 kDa-interacting protein 3 (BNIP3) represents a paradigm of a cell death protein that is hypoxically upregulated via HIF-1 in most cancers. We found that in contrast to many other cell types, 6/8 colorectal cancer (CRC) cell lines show little hypoxic induction of BNIP3 despite an intact HIF signalling system. Colorectal tumour tissue also loses BNIP3 expression relative to matched normal samples. Downregulation of hypoxic BNIP3 in CRC cells was independent of the expression of other BCL-2 family members, or BNIP3L. That BNIP3 plays a functional role in hypoxic survival in CRC cells was demonstrated by the fact that CRC cell lines that do not upregulate BNIP3 or have been treated with BNIP3 RNA interference were insensitive to hypoxia-induced cell death. Promoter methylation and histone deacetylation were shown to silence BNIP3 in these CRC cell lines. Of significance, hypoxic induction of BNIP3 was restored in 4/6 cell lines by trichostatin-A treatment alone. These data suggest that BNIP3 plays an important role in hypoxic cell death and epigenetic mechanisms selectively silence its expression in CRC.

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“…A number of reports have demonstrated that the probability of distant metastases correlates with oxygen pressure in the tumour tissues (Gatenby et al, 1988;Brizel et al, 1996;Hockel et al, 1998;Rofstad, 2000), suggesting that hypoxia may promote metastatic potential. However, it remains poorly understood how hypoxia promotes the metastatic potential of tumour cells.…”

Section: Discussionmentioning

confidence: 99%

“…Although a variety of factors have been documented to play important roles in the metastatic steps (Poste and Fidler, 1980;Liotta, 1986Liotta, , 1988Nicolson, 1988), many factors are yet to be elucidated. Several clinical investigations demonstrated that patients with hypoxic tumours had poor prognoses and that the incidence of distant metastases was higher in the tumours with low oxygen pressure than in those with high oxygen pressure (Gatenby et al, 1988;Brizel et al, 1996;Hockel et al, 1998;Rofstad, 2000). These studies suggest that the tumour cells exposed to hypoxia at the primary tumour sites acquire aggressive properties including metastatic potential more than the welloxygenated tumour cells do.…”

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confidence: 99%

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

et al. 2002

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The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1a, we established hypoxia-inducible factor-1a-transfectants and dominant negative hypoxiainducible factor-1a-transfectants. Transfection with hypoxia-inducible factor-1a and dominant-negative hypoxia-inducible factor-1a enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis. As metastasis is the major cause of death in cancer patients, control of metastasis is most important in the therapies for cancer patients. In order to control metastasis, we need to understand the details of metastatic process that is now thought to take multiple steps. Although a variety of factors have been documented to play important roles in the metastatic steps (Poste and Fidler, 1980;Liotta, 1986Liotta, , 1988Nicolson, 1988), many factors are yet to be elucidated. Several clinical investigations demonstrated that patients with hypoxic tumours had poor prognoses and that the incidence of distant metastases was higher in the tumours with low oxygen pressure than in those with high oxygen pressure (Gatenby et al, 1988;Brizel et al, 1996;Hockel et al, 1998;Rofstad, 2000). These studies suggest that the tumour cells exposed to hypoxia at the primary tumour sites acquire aggressive properties including metastatic potential more than the welloxygenated tumour cells do. In fact, recent reports have demonstrated that hypoxia enhances the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in tumour cells, resulting in an increase of metastatic potential (Claffey and Robinson, 1996;Shi et al, 1999;Biroccio et al, 2000). However, it remains poorly understood how hypoxia promotes tumour cells' metastatic potential.When tumour cells are exposed to hypoxia, hypoxia-inducible factor-1 (HIF-1), which is a transcription factor composed of HIF-1a and HIF-1b subunits (Wang et al,...

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Tumor hypoxia in pelvic recurrences of cervical cancer

Cited by 163 publications

References 17 publications

Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

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