Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | PANC-1(RCB2095) |