Laminin α5 mediates ectopic adhesion of hepatocellular carcinoma through integrins and/or Lutheran/basal cell adhesion molecule

Yamato Kikkawa, Ryo Sudo, Junko Kon, Toru Mizuguchi, Motoyoshi Nomizu, Koichi Hirata, Toshihiro Mitaka

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Laminins are a diverse group of α/β/γ heterotrimers formed from five α, three β and three γ chains; they are major components of all basal laminae (BLs). One laminin chain that has garnered particular interest due to its widespread expression pattern and importance during development is laminin α5. Little is known, however, about the expression and function of laminins containing the α5 chain in human hepatocellular carcinoma (HCC). Here, using a specific antibody, we examined the expression of laminin α5 in normal liver and in HCCs. In normal liver, although laminin α5 was observed in hepatic BLs underlying blood vessels and bile ducts, it was absent from the parenchyma, which may be the origin of HCC. On the other hand, laminin α5 deposition was observed throughout all HCCs tested, regardless of tumor grade. In well-differentiated HCCs, it localized along the trabecules of the tumor. In poorly-differentiated HCCs, it was present in surrounding tumor nodules. In HCC cell lines, laminin α5 heterotrimerized with β and γ chains and was secreted into the culture media. To attempt to understand the function of laminins containing α5, the expression of its receptors in HCCs was also determined. In this regard, α3β1/α6β1 integrins and Lutheran/basal cell adhesion molecule (Lu/B-CAM) were expressed in HCC cells. In vitro studies showed that HCC cells readily attached to laminin containing the α5 chain, more so than did primary hepatocytes. In addition to α3β1/α6β1 integrins and Lu/B-CAM, laminin α5 was recognized by integrin α1β1, which also was expressed in HCC cells. These results suggest that laminins containing α5 serve as functional substrates regulating progression of HCC.

Original languageEnglish
Pages (from-to)2579-2590
Number of pages12
JournalExperimental Cell Research
Volume314
Issue number14
DOIs
Publication statusPublished - 2008 Aug 15

Keywords

  • Basal cell adhesion molecule
  • Hepatocellular carcinoma
  • Integrin
  • Laminin
  • Lutheran

ASJC Scopus subject areas

  • Cell Biology

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