RRC ID 54074
著者 Okumura T, Ohuchida K, Kibe S, Iwamoto C, Ando Y, Takesue S, Nakayama H, Abe T, Endo S, Koikawa K, Sada M, Horioka K, Mochidome N, Arita M, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
タイトル Adipose tissue-derived stromal cells are sources of cancer-associated fibroblasts and enhance tumor progression by dense collagen matrix.
ジャーナル Int J Cancer
Abstract Although recent studies revealed that adipose tissue accelerates pancreatic tumor progression with excessive extracellular matrix, key players for desmoplasia in the adipose microenvironment remains unknown. Here, we investigated the roles of adipose tissue-derived stromal cells (ASCs) in desmoplastic lesions and tumor progression by in vitro and in vivo experiments. In a three-dimensional (3-D) organotypic fat invasion model using visceral fat from CAG-EGFP mice, GFP-positive fibroblastic cells infiltrated toward cancer cells. When tumor cells were inoculated into transplanted visceral fat pads in vivo, tumor weights and stromal components were enhanced compared to subcutaneous and orthotopic tumor cells inoculated without fat pads. Expression of αSMA in established human ASCs was lower compared to cancer associated fibroblasts, and the 3-D collagen matrices produced by ASCs cultured in cancer cell-conditioned medium changed from loose to dense structures that affected the motility of cancer cells. Microarray analyses revealed upregulation of S100A4 in ASCs, while S100A4-positive stromal cells were observed at extrapancreatic invasion sites of human pancreatic cancer. The present findings indicate that ASCs are recruited to extrapancreatic invasion sites and produce dense collagen matrices that lead to enhanced tumor progression. Both inhibition of ASCs recruitment and activation could lead to a novel antistromal therapy.
巻・号 144(6)
ページ 1401-1413
公開日 2019-3-15
DOI 10.1002/ijc.31775
PMID 30152542
MeSH Actins / metabolism Aged Animals Cancer-Associated Fibroblasts / pathology* Carcinoma, Pancreatic Ductal / pathology* Carcinoma, Pancreatic Ductal / surgery Cell Differentiation Collagen / metabolism* Culture Media, Conditioned / metabolism Disease Progression Extracellular Matrix / metabolism Extracellular Matrix / pathology Female Humans Intra-Abdominal Fat / cytology Intra-Abdominal Fat / transplantation Male Mice, Inbred C57BL Mice, Nude Mice, Transgenic Middle Aged Pancreatic Neoplasms / pathology* Pancreatic Neoplasms / surgery Primary Cell Culture S100 Calcium-Binding Protein A4 / metabolism Stromal Cells / pathology* Tumor Cells, Cultured Tumor Microenvironment
IF 5.145
引用数 4
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)