Details

Autor(en) / Beteiligte

• Sano, Makoto
• Ijichi, Hideaki
• Takahashi, Ryota
• Miyabayashi, Koji
• Fujiwara, Hiroaki
• Yamada, Tomoharu
• Kato, Hiroyuki
• Nakatsuka, Takuma
• Tanaka, Yasuo
• Tateishi, Keisuke
• Morishita, Yasuyuki
• Moses, Harold L
• Isayama, Hiroyuki
• Koike, Kazuhiko

Titel

Blocking CXCLs-CXCR2 axis in tumor-stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment

Ist Teil von

• Oncogenesis (New York, NY), 2019-01, Vol.8 (2), p.8-8, Article 8

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stromal reaction (desmoplasia). We have previously reported that mice with conditional Kras mutation and knockout of TGF-β receptor type II (Tgfbr2), PKF mice, develop PDAC with desmoplasia modulated by CXC chemokines that are produced by PDAC cells through tumor-stromal interaction. In this study, we further discovered that PDAC and cancer-associated fibroblast (CAF) accelerated each other's invasion and migration through the CXC chemokines-receptor (CXCLs-CXCR2) axis. Heterozygous knockout of Cxcr2 in PKF mice (PKF2h mice) prolonged survival and inhibited both tumor angiogenesis and PDAC microinvasion. Infiltration of neutrophils, myeloid-derived suppressor cells (MDSCs), and arginase-1 M2-like tumor-associated macrophages (TAMs) significantly decreased in the tumors of PKF2h mice, whereas inducible nitric oxide synthase (iNOS) M1-like TAMs and apoptotic tumor cells markedly increased, which indicated that blockade of the CXCLs-CXCR2 axis resulted in a shift of immune-inflammatory microenvironment. These results suggest that blocking of the CXCLs-CXCR2 axis in tumor-stromal interactions could be a therapeutic approach against PDAC progression.