Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells.
OBJECTIVE
A correlation between overexpression of tetraspanin CO-029 and the intrahepatic spread of hepatocellular carcinoma (HCC) has been observed in surgically resected specimens from humans. However, the cellular mechanisms involved in CO-029 protein modulation of the metastatic phenotype are unknown. In the present study, CO-029 cDNA was stably transfected into a non-metastatic human HCC cell line to investigate whether it could directly promote metastasis.


METHODS
We constructed a human HCC cell line that stably overexpressed CO-029 and mock transfectants. Using these transfectants, we examined cell proliferation characteristics in monolayer culture and the ability to adhere to culture plates coated with laminin, fibronectin, vitronectin and collagen type-I or type-IV. Orthotopic implantation of these transfectants to SCID mice was also performed.


RESULTS
Several clones of CO-029 transfectants and mock transfectants were established. The growth rates and adhesive properties to the extracellular matrix did not differ between CO-029 and mock transfectants. When orthotopically implanted, the size of the primary tumor in the liver did not differ between CO-029 and the mock transfectants. However, only CO-029 positive clones developed intrahepatic metastatic lesions.


CONCLUSIONS
These results suggest that CO-029 might be involved in hematogenous intrahepatic metastasis, although the precise cellular mechanisms involved remain unknown.
Kanetaka
Kengo
K
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Sakamoto
Michiie
M
Yamamoto
Yoshiya
Y
Takamura
Masaaki
M
Kanematsu
Takashi
T
Hirohashi
Setsuo
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000556:secondary*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009368:Neoplasm Transplantation; D059470:Tetraspanins
D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; C065609:TSPAN8 protein, human; D059470:Tetraspanins