title: 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: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. Electronic address: kikkawa@toyaku.ac.jp.
authors: Yamato
authors: Y
authors: Kikkawa
authors: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Miwa
authors: Department of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors: Naoki
authors: N
authors: Tanimizu
authors: Department of Anatomy, Kitasato University School of Allied Health Sciences, Minami-ku, Sagamihara, Japan.
authors: Yuichi
authors: Y
authors: Kadoya
authors: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Takaho
authors: T
authors: Ogawa
authors: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Fumihiko
authors: F
authors: Katagiri
authors: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Kentaro
authors: K
authors: Hozumi
authors: Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Motoyoshi
authors: M
authors: Nomizu
authors: Department of 1st Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Toru
authors: T
authors: Mizuguchi
authors: Department of 1st Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Koichi
authors: K
authors: Hirata
authors: Department of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors: Toshihiro
authors: T
authors: Mitaka
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008188:Lutheran Blood-Group System / Q000378:metabolism*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C090228:BCAM protein, human; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D007797:Laminin; D008188:Lutheran Blood-Group System; D034741:RNA, Small Interfering; C551997:laminin-511, human; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Basal cell adhesion molecule; Hepatocellular carcinoma; Laminin; Lutheran; MMP