Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor

Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Chen, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

doi:10.1016/j.jss.2012.06.051

Cited by 42 publications

(28 citation statements)

References 36 publications

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“…It has been shown that cancer-associated PaSCs in hypoxia enhance the invasion of cancer cells more strongly than those in normoxia, with carbonic anhydrase 9 (CA9) being a useful hypoxic-regulated marker (as well as HIF-1 a) [55]. As expected VEGF expression was increased (4.5 fold) in hypoxia as compared to normoxia, however the role of connective tissue growth factor (CTGF) was elucidated.…”

Section: Angiogenesismentioning

confidence: 83%

The role of pancreatic stellate cells in pancreatic cancer

2015

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Section: Angiogenesismentioning

confidence: 83%

The role of pancreatic stellate cells in pancreatic cancer

2015

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“…Pancreatic tumors are hypovascular, and cancer cells are thought to thrive under hypoxic conditions. In an in vitro study, Eguchi et al 17 showed that the effect of PaSCs on cancer cell invasion is significantly greater under hypoxic (1% oxygen) than normoxic (21% oxygen) conditions. Hypoxia was shown to increase secretion of connective tissue growth factor (CTGF) by PaSCs, and knockdown of CTGF in PaSCs reduced cancer cell invasion under hypoxic conditions.…”

Section: Interactions Between Pasc and Cancer Cells In Culturementioning

confidence: 99%

A Starring Role for Stellate Cells in the Pancreatic Cancer Microenvironment

et al. 2013

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Pancreatic ductal adenocarcinoma is a devastating disease, and patient outcomes have not improved in decades. Treatments that target tumor cells have largely failed. This could be because research has focused on cancer cells and the influence of the stroma on tumor progression has been largely ignored. The focus of pancreatic cancer research began to change with the identification of pancreatic stellate cells, which produce the pancreatic tumor stroma. There is compelling in vitro and in vivo evidence for the influence of pancreatic stellate cells on pancreatic cancer development; several recent preclinical studies have reported encouraging results with approaches designed to target pancreatic stellate cells and the stroma. We review the background and recent advances in these areas, along with important areas of future research that could improve therapy.

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“…We examined by RT-PCR whether the expressions of the motility-and invasion-related genes, which are reported to be upregulated in HIF-1-mediated manner, and other genes relevant to them underwent changes in hypoxia [4,[19][20][21][22][23][24]. As shown in Fig.4, the expression of MUC1 gene increased in all the MPM cell lines when they were under hypoxia, but no common change was observed among the cell lines in the expressions of other genes whether they were under hypoxia or normoxia.…”

Section: Muc1 Possibly a Hif-1 Target Gene Involved In Hypoxia-enhanmentioning

confidence: 99%

Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway

et al. 2013

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In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found 1) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; 2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; 3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients.

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Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor

Cited by 42 publications

References 36 publications

The role of pancreatic stellate cells in pancreatic cancer

The role of pancreatic stellate cells in pancreatic cancer

A Starring Role for Stellate Cells in the Pancreatic Cancer Microenvironment

Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway

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