Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer–stromal interactions in a mouse xenograft model
Year: 2016
Type: article
Abstract: Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several antifibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of desmoplasia-targeting antifibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model. We used quantitative RT-PCR to evaluate the expression of calpain-1 and calpain-2 mRNA in pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs). We also undertook functional assays, including proliferation, migration, and invasion, to evaluate the inhibitory effects of calpeptin on PCCs and PSCs. Quantitative RT-PCR indicated that PCCs and PSCs expressed calpain-2 mRNA. Calpeptin reduced tumor volume (P = 0.0473) and tumor weight (P = 0.0471) and inhibited the tumor desmoplastic reaction (P < 0.001) in xenograft tumors in nude mice. Calpeptin also inhibited the biologic functions of PCCs and PSCs including proliferation (P = 0.017), migration (P = 0.027), and invasion (P = 0.035) in vitro. Furthermore, calpeptin reduced the migration of PCCs and PSCs by disrupting the cancer-stromal interaction (P = 0.0002). Our findings indicate that calpeptin is a promising antitumor agent for pancreatic cancer, due not only to its suppressive effect on PCCs and PSCs but also its disruption of the cancer-stromal interaction.
Source: Cancer Science
DOI: 10.1111/cas.13024
Authors: Masaki Yoshida, Yoshihiro Miyasaka, Kenoki Ohuchida, Takashi Okumura, Biao Zheng, Nobuhiro Torata, Hayato Fujita, Toshinaga Nabae, Tatsuya Manabe, Masaya Shimamoto, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura
Institutions: Kyushu University, Kyushu University Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,600
Awards: G297644444, Nobel role of liver endothelial cells in liver metastasis formation, G3296525006, Elucidation of leading cell and cancer microenvironment normalization of pancreatic cancer, Identification of pancreatic cancer specific metabolites by metabolome mapping and application possibility for diagnostic biomarker., Regulation of extracellular matrix remodeling induced by stellate cells and immune cells in the pancreatic tumor microenvironment, The development of pancreatic cancer therapy based on regulating extracellular matrix remodeling by pancreatic stellate cells, A new strategy in the treatment of pancreatic cancer focused on the tumor vessel remodeling by pericytes, Induction of tumor-suppressing pancreatic stellate cell subpopulation by pancreatic cancer microenvironment reprogramming, Normalization of tumor vessels targeting pericytes; a new approach in treatment of pancreatic cancer, Elucidation and control of the microemviroment of pancreatic cancer, Early detection of pancreatic ductal adenocarcinoma based on the molecular assessment of pancreatic ductal adenocarcinoma concomitant with IPMN of the pancreas., Management of pancreatic cancer liver metastasis through investigating the mechanism of formation and remodeling its microenvironment.
OpenAlex ID: W2485565959