[Laminin and its alpha 6 integrin receptor in the regulation of human hepatocellular carcinoma cell phenotypes].
OBJECTIVE
To study the role of integrin alpha 6 in cell attachment, spread, survival/proliferation and differentiation of human hepatocellular carcinoma (HCC) BEL-7402 cells on various substrates by monoclonal antibody against the extracellular domain of alpha 6 subunit (IA6ED McAb).


METHODS
The effect of McAb on attachment and spread of BEL-7402 cells on LN or FN substrate was examined. MTT analysis was used to examine the cell survival/proliferation, gelatin zymography to the matrix metalloproteinases (MMPs) secreted by BEL-7402 cells, and microparticle immunoabsorbent kit to AFP secretion while the cells were cultured on LN-, FN- or Matrigel-coated substrates.


RESULTS
The cell attachment, spread and survival/proliferation were inhibited. Moreover importantly, the malignant cell dedifferentiation and abnormal differentiation on LN-coated substrate were also strongly inhibited by IA6ED McAb.


CONCLUSIONS
LN and integrin alpha 6 regulate human HCC cell phenotypes of survival/proliferation and differentiation. The phenotypes of dedifferentiation and abnormal differentiation can be reversed by blocking the interaction between integrin alpha 6 and LN using IA6ED McAb, which may lower metastatic potency of tumor cells.
Lu
Tian-jing
TJ
Department of Cell Biology, School of Basic Medical Sciences, Beijing 100083, China.
Zhang
Qing-yun
QY
Zhou
Rou-li
RL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D039503:Integrin alpha6 / Q000276:immunology / Q000502:physiology*; D007797:Laminin / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology; D010641:Phenotype; D017474:Receptors, Laminin / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D039503:Integrin alpha6; D007797:Laminin; D017474:Receptors, Laminin