KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97-H cells in vitro and in animal models.
BACKGROUND
Downregulation of KAI1 gene expression has been found in many types of cancer cells and is closely related to cancer invasion and metastasis. This study was aimed at investigating the effects and possible underlying mechanisms of KAI1 gene on invasion and metastasis of human hepatocellular carcinoma (HCC).


METHODS
The invasive ability, visco-elastic properties and cell adhesion forces were analysed in different HCC cells originating from the MHCC97-H cell line transfected with either the sense or the antisense KAI1 expression plasmid. Tumuorigenicity, metastatic abilities, extracellular matrix (ECM) and intercellular adhesion molecule-1 (ICAM-1) expression were also evaluated in the nude mouse models of the xenografted and orthotopic liver cancer cells.


RESULTS
Compared with their parental cells, in the HCC cells transfected with the sense KAI1 gene, the invasive ability in vitro was significantly decreased (P<0.01); the cellular elastic coefficients K(1), K(2) and mu were significantly higher (P<0.05); the cells adhesion forces to fibronectin were significantly lower (P<0.01). The sense KAI1 gene transfection into the cancer cells also inhibited their invasion and lung metastasis in the orthotopic liver cancer nude mice. However, the opposite changes were observed in the HCC cells transfected with the antisense KAI1 gene. KAI1 gene transfection also affected ECM and ICAM-1 expression in the transplanted liver cancer.


CONCLUSIONS
The KAI1 gene plays an important role in the invasion and metastasis of human HCC and its upregulation in HCC cells suppresses their invasive and metastatic abilities. KAI1 gene functioned as a metastasis inhibitor by regulating the HCC cell biophysical behaviours including aggregation, adhesion, motility and visco-elastic properties.
Yang
Jian-Min
JM
Zhejiang Provincial Key Gastroenterology Laboratory, Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, China. jianminyang@hotmail.com
Peng
Zhi-Hong
ZH
Si
Sui-Hai
SH
Liu
Wei-Wen
WW
Luo
Yuan-Hui
YH
Ye
Zai-Yuan
ZY
D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D014162:Transfection
C497688:CD82 protein, human; D051861:Kangai-1 Protein