Soluble Lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro.

Abstract

Lutheran (Lu), an immunoglobulin superfamily transmembrane receptor, is also known as basal cell adhesion molecule (B-CAM). Lu/B-CAM is a specific receptor for laminin α5, a subunit of laminin-511 (LM-511) that is a major component of basement membranes in various tissues. Our previous study showed that Lu/B-CAM was cleaved by MT1-MMP and released from cell surfaces. In this study we examined the soluble Lu/B-CAM in culture media and in plasma of mice bearing HuH-7 hepatocellular carcinoma (HCC) cells and patients with HCC. Two HCC cell lines, HepG2 and HuH-7, released Lu/B-CAM into the culture media. Although Lu/B-CAM was cleaved by MT1-MMP in HuH-7 cells, HepG2 cells released Lu/B-CAM in a MMP-independent manner. The concentration of Lu/B-CAM released into mouse plasma correlated with tumor size. Moreover the soluble Lu/B-CAM in plasma of HCC patients was significantly decreased after resection of the tumor. Immunohistochemical studies showed that although the expression of Lu/B-CAM was observed in most HCCs, MT1-MMP was not always expressed in tumor tissues, suggesting that a part of Lu/B-CAM in plasma of HCC patients was also released in a MMP-independent manner. In vitro studies showed that the soluble Lu/B-CAM released from HCC cells bound to LM-511. Moreover the soluble Lu/B-CAM influenced cell migration on LM-511. These results suggest that soluble Lu/B-CAM serves as not only a novel marker for HCC but also a modulator in tumor progression.

• Authors: Yamato Kikkawa, Takahiro Miwa, Naoki Tanimizu, Yuichi Kadoya, Takaho Ogawa, Fumihiko Katagiri, Kentaro Hozumi, Motoyoshi Nomizu, Toru Mizuguchi, Koichi Hirata, Toshihiro Mitaka
• Journal: Experimental cell research (Exp Cell Res) Vol. 328 Issue 1 Pg. 197-206 (Oct 15 2014) ISSN: 1090-2422 [Electronic] United States
• PMID: 25051049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• BCAM protein, human
• Biomarkers, Tumor
• Cell Adhesion Molecules
• Laminin
• Lutheran Blood-Group System
• RNA, Small Interfering
• laminin-511, human
• MMP14 protein, human
• Matrix Metalloproteinase 14

Topics

• Adult
• Aged
• Animals
• Biomarkers, Tumor (blood)
• Blotting, Western
• Carcinoma, Hepatocellular (metabolism, pathology, surgery)
• Cell Adhesion Molecules (metabolism)
• Cell Movement
• Cell Proliferation
• Female
• Flow Cytometry
• Glycosylation
• Humans
• Immunoenzyme Techniques
• Immunoprecipitation
• In Vitro Techniques
• Laminin (metabolism)
• Liver Neoplasms (metabolism, pathology, surgery)
• Lutheran Blood-Group System (metabolism)
• Male
• Matrix Metalloproteinase 14 (chemistry, genetics, metabolism)
• Mice
• Mice, Nude
• Middle Aged
• Protein Interaction Domains and Motifs
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured