| RRC ID |
72842
|
| Author |
Ohuchida K, Mizumoto K, Murakami M, Qian LW, Sato N, Nagai E, Matsumoto K, Nakamura T, Tanaka M.
|
| Title |
Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions.
|
| Journal |
Cancer Res
|
| Abstract |
Radiotherapy represents a major treatment option for patients with pancreatic cancer, but recent evidence suggests that radiation can promote invasion and metastasis of cancer cells. Interactions between cancer cells and surrounding stromal cells may play an important role in aggressive tumor progression. In the present study, we investigated the invasive phenotype of pancreatic cancer cells in response to coculture with irradiated fibroblasts. Using in vitro invasion assay, we demonstrated that coculture with nonirradiated fibroblasts significantly increased the invasive ability of pancreatic cancer cells and, surprisingly, the increased invasiveness was further accelerated when they were cocultured with irradiated fibroblasts. The hepatocyte growth factor (HGF) secretion from fibroblasts remained unchanged after irradiation, whereas exposure of pancreatic cancer cells to supernatant from irradiated fibroblasts resulted in increased phosphorylation of c-Met (HGF receptor) and mitogen-activated protein kinase activity, possibly or partially via increased expression of c-Met. We also demonstrated that scattering of pancreatic cancer cells was accelerated by the supernatant from irradiated fibroblasts. The enhanced invasiveness of pancreatic cancer cells induced by coculture with irradiated fibroblasts was completely blocked by NK4, a specific antagonist of HGF. These data suggest that invasive potential of certain pancreatic cancer cells is enhanced by soluble mediator(s) released from irradiated fibroblasts possibly through up-regulation of c-Met expression/phosphorylation and mitogen-activated protein kinase activity in pancreatic cancer cells. Our present findings further support the potential use of NK4 during radiotherapy for patients with pancreatic cancer.
|
| Volume |
64(9)
|
| Pages |
3215-22
|
| Published |
2004-5-1
|
| DOI |
10.1158/0008-5472.can-03-2464
|
| PMID |
15126362
|
| MeSH |
Cell Communication / physiology
Cell Communication / radiation effects*
Cell Line, Tumor
Coculture Techniques
Fibroblasts / metabolism
Fibroblasts / radiation effects*
Growth Substances / metabolism
Hepatocyte Growth Factor / biosynthesis
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / pharmacology
Humans
Mitogen-Activated Protein Kinases / metabolism
Mitogens*
Neoplasm Invasiveness
Pancreatic Neoplasms / enzymology
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology*
Phosphorylation
Proto-Oncogene Proteins c-met / biosynthesis
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins c-met / metabolism
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Stromal Cells / metabolism
Stromal Cells / radiation effects
|
| IF |
9.727
|
| Resource |
| Human and Animal Cells |
MRC-5(RCB0211) |
