RRC ID 52428
著者 Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
タイトル Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180.
ジャーナル Cancer Lett
Abstract Specific cell populations leading the local invasion of cancer are called "leading cells". However, the underlying mechanisms are unclear. Here, we identified leading cells in pancreatic cancer and determined how these cells lead and promote cancer cell invasion in the extracellular matrix (ECM). Using three-dimensional matrix remodeling assay, we found that pancreatic stellate cells (PSCs) frequently invaded the collagen matrix with pancreatic cancer cells (PCCs), which invaded behind the invading PSCs. In addition, invading PSCs changed the alignment of collagen fibers, resulting in ECM remodeling and an increase in the parallel fibers along the direction of invading PSCs. Endo180 expression was higher in PSCs than in PCCs, Endo180 knockdown in PSCs attenuated the invasive abilities of PSCs and co-cultured PCCs, and decreased the expression level of phosphorylated myosin light chain 2 (MLC2). In mouse models, Endo180-knockdown PSCs suppressed tumor growth and changes in collagen fiber orientation in co-transplantation with PCCs. Our findings suggest that PSCs lead the local invasion of PCCs by physically remodeling the ECM, possibly via the function of Endo180, which reconstructs the actin cell skeleton by phosphorylation of MLC2.
巻・号 412
ページ 143-154
公開日 2018-1-1
DOI 10.1016/j.canlet.2017.10.010
PII S0304-3835(17)30644-4
PMID 29061505
MeSH Cardiac Myosins / metabolism Cell Line, Tumor Collagen / chemistry Extracellular Matrix / chemistry* Humans Myosin Light Chains / metabolism Neoplasm Invasiveness Pancreatic Neoplasms / pathology* Pancreatic Stellate Cells / physiology* Phosphorylation Receptors, Mitogen / physiology*
IF 7.36
引用数 12
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)