| Literature DB >> 29580808 |
Kazuhiro Koikawa1, Kenoki Ohuchida2, Yohei Ando1, Shin Kibe1, Hiromichi Nakayama1, Shin Takesue1, Sho Endo1, Toshiya Abe1, Takashi Okumura1, Chika Iwamoto3, Taiki Moriyama1, Kohei Nakata1, Yoshihiro Miyasaka1, Takao Ohtsuka1, Eishi Nagai1, Kazuhiro Mizumoto1, Makoto Hashizume3, Masafumi Nakamura4.
Abstract
Stroma invasion is an important step in pancreatic cancer progression. However, how pancreatic ductal adenocarcinoma (PDAC) with ductal structure invades the surrounding stroma has not been clear. Here, we elucidated the mechanism of stromal invasion of PDAC, using organoids. From resected PDAC specimens, we established human PDAC organoids, which developed ductal and basement membrane (BM) structures. When the organoids were co-cultured with pancreatic stellate cells (PSCs) in a collagen matrix, organoids lost their BM and ductal structures, and invaded collagen matrix more frequently than did mono-cultured organoids. Interestingly, direct contact by PSCs to PDAC organoids was observed before BM destruction. Matrix metalloproteinase (MMP) 2 or membrane type-1 MMP (MT1MMP) knockdown in PSCs significantly attenuated BM destruction by PSCs, and retained the ductal structures in organoids. Our results imply that direct contact by PSCs induces BM destruction and stromal invasion of PDAC via MMP2 which binds to MT1MMP on PSCs.Entities:
Keywords: Basement membrane destruction; MMP2; MT1MMP; Organoid; Pancreatic cancer; Pancreatic stellate cells
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Year: 2018 PMID： 29580808 DOI： 10.1016/j.canlet.2018.03.031
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679