Laminin induces the expression of cytokeratin 19 in hepatocellular carcinoma cells growing in culture.
OBJECTIVE
To study the abnormal cytokeratin (CK) expression, emergence of CK19 with or without CK7, in liver parenchymal cells and the role of laminin (LN), a basement membrane protein, in this process.


METHODS
Six hepatocellular carcinoma (HCC) cell lines were examined for different CKs, LN and its receptor by immunocytochemistry and Western blotting. Double immunofluorescent reaction, laser-scanning confocal microscopy and an in vitro induction procedure were used to demonstrate the role of LN in regulating CK19 expression in these cells.


RESULTS
Immunoreactivities for CK8, CK18, CK7 and the receptor for LN were observed in all the six HCC cell lines examined. However, CK19 was merely found in four of the six cell lines, and was in any case associated with LN expression. Laser-scanning confocal microscopy demonstrated the concomitant presence of these two molecules in most of the positive cells. In the two HCC cell lines, originally negative for CK19, addition of LN to the culture medium resulted in an induction of CK19 in a dose-dependent manner. Both the artificially induced and the intrinsic production of CK19 were completely blocked by an antibody to LN.


CONCLUSIONS
LN can induce expression of CK19 in HCC cells in vitro, providing direct evidence for our hypothesis that the abnormal hepatocytic CK19 expression in situ is due to pathologic LN deposition.
Su
Qin
Q
Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China. qinsu@fmmu.edu.cn
Fu
Yong
Y
Liu
Yan-Fang
YF
Zhang
Wei
W
Liu
Jie
J
Wang
Chun-Mei
CM
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D017474:Receptors, Laminin / Q000378:metabolism; D014407:Tumor Cells, Cultured
C507497:KRT7 protein, human; D053552:Keratin-7; D007797:Laminin; D017474:Receptors, Laminin; D007633:Keratins