Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an adhesion molecule of the immunoglobulin superfamily, has been characterized as a putative tumor suppressor because it is frequently down-regulated in aggressive types of cancer cells. Recently, however, several studies have shown that CEACAM1 actively contributes to malignant progression or migration in some types of tumor cells, suggesting that the role of CEACAM1 might be diverse among different types of cancer cells. To investigate the functional consequences of CEACAM1 expression in hepatocellular carcinoma, we analyzed the status of CEACAM1 in hepatoma cell lines HLF, PLC/PRF/5, HepG2 and KYN-2. We found that CEACAM1 was only expressed in HepG2 cells, which show a unique property for enhanced anchorage-independent growth. When HepG2 cells were treated with small interfering RNA targeted against CEACAM1, the growth rate in monolayer culture was increased. In contrast, when HepG2 cells were cultured in suspension, inhibition of CEACAM1 expression significantly decreased the growth rate, and the speed of cell-cell attachment was repressed. Hyaluronidase treatment attenuated the growth rate of HepG2 cells in suspension culture, indicating that cell-cell attachment is a requisite for anchorage-independent growth. Our data may reveal the dual role of CEACAM1 on hepatocarcinogenesis, by showing that CEACAM1 acts as a tumor suppressor in HepG2 cells in anchorage-dependent growth conditions, while in anchorage-independent growth conditions, it augments cell proliferation by potentiating the cell-cell attachment.
Hokari
Mariko
M
Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan.
Matsuda
Yasunobu
Y
Wakai
Toshifumi
T
Shirai
Yoshio
Y
Sato
Munehiro
M
Tsuchiya
Atsunori
A
Takamura
Masaaki
M
Yamagiwa
Satoshi
S
Suzuki
Kenji
K
Ohkoshi
Shogo
S
Ichida
Takafumi
T
Kawachi
Hiroshi
H
Aoyagi
Yutaka
Y
D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism*
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins