| RRC ID |
63417
|
| Author |
Sada M, Ohuchida K, Horioka K, Okumura T, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Nakamura M.
|
| Title |
Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.
|
| Journal |
Cancer Lett
|
| Abstract |
Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer.
|
| Volume |
372(2)
|
| Pages |
210-8
|
| Published |
2016-3-28
|
| DOI |
10.1016/j.canlet.2016.01.016
|
| PII |
S0304-3835(16)00028-8
|
| PMID |
26805763
|
| MeSH |
Cell Hypoxia
Cell Movement*
Extracellular Matrix / metabolism
Extracellular Matrix / pathology*
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Invasiveness
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology*
Pancreatic Stellate Cells / metabolism
Pancreatic Stellate Cells / pathology*
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / metabolism
RNA Interference
Stromal Cells / metabolism
Stromal Cells / pathology*
Time Factors
Transfection
Tumor Cells, Cultured
Tumor Microenvironment*
|
| IF |
7.36
|
| Resource |
| Human and Animal Cells |
PANC-1(RCB2095) |
