Abstract 1429: Contribution of membrane-bound carboxypeptidase M to tumor growth and metastasis by regulating epithelial mesenchymal transition in esophageal squamous carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 75; no. 15_Supplement; p. 1429
• Main Authors: Kudo, Yuji, Fukuda, Junki, Harigai, Ritsuko, Kato, Kazunori
• Format: Journal Article
• Language: English
• Published: 01.08.2015
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-1429

Abstract Carboxypeptidase M (CPM) is a membrane-bound exopeptidase that recognizes the arginine (Arg) and lysine (Lys) residues in a C-terminal of polypeptide chain or protein. The cleavage of some soluble factors such as SDF-1 and EGF by CPM leads to the alteration of binding affinity to their receptors. In this study, we examined the properties of CPM for tumor growth and metastasis in human esophageal carcinoma cells. In order to investigate the expression of CPM on human tumor cells, we established the monoclonal antibody specific for human CPM and found the constitutive expression of CPM on various human carcinomas by flow cytometry and confocal laser microscopy. Treatment of cancer cells with EMT-mediated cytokines, including TGF-beta, IL-6 and OSM, increased CPM expression on their cell surface followed by enhancement of cell migration and change of cell shapes from epithelial to mesenchymal type. Silencing CPM expression by small interfering RNA (siRNA) specific for CPM in esophageal and breast carcinoma cells were confirmed by flow cytometry. We found that CPM-silenced carcinoma exhibited reduced cell proliferation not only in 2D culture flask but also in 3D spheroid culture plate. Importantly, the treatment of siRNA for CPM inhibited the expression of EMT-related genes such as snail and slug which are important for cancer motility. Consistently, we found that CPM-silenced carcinoma exhibited reduced motility of cell in wound healing assay. Taken together, these data indicate that CPM contributes to cell growth and EMT and might be a therapeutic target in esophageal carcinoma. Citation Format: Yuji Kudo, Junki Fukuda, Ritsuko Harigai, Kazunori Kato. Contribution of membrane-bound carboxypeptidase M to tumor growth and metastasis by regulating epithelial mesenchymal transition in esophageal squamous carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1429. doi:10.1158/1538-7445.AM2015-1429