Interactions between endothelial and tumor cells via E-selectin and sialyl Lewis x (sLex) have been suggested to play a significant role in the development of metastasis and tumor growth. In this work, we tested whether inhibition of E-selectin expression on the surface of endothelial cells might impair endothelial/tumor cells interactions and tumor growth of hepatocarcinoma cells in vitro and in vivo. We used HepG2 cells that highly express sLex antigens and HuH7 cells that do not express sLex. Inhibition of E-selectin expression on the surface of endothelial cells was obtained by using cimetidine and amiloride treatment. Cimetidine and amiloride inhibited, respectively, by 20 and 64 % E-selectin expression by activated endothelial cells and significantly subsequent adhesion of HepG2 cells to activated endothelial cells. Subcutaneous injection of cimetidine or amiloride resulted in a significant inhibition of HepG2 cells tumor growth in nu/nu mice but not of HuH7 cells. Thus, cimetidine and amiloride administration led to an inhibition of 57 and 75 % of HepG2 tumor growth in vivo, respectively. This effect was associated with an inhibition of vasculogenesis as demonstrated by anti-CD31 immunostaining. Inhibition of E-selectin expression allows an anti-tumoral effect on sLex-expressing HCC tumors in vivo. This suggests that interactions between HCC cells and endothelial cells through sLex antigens and E-selectin might be a target for treatment of HCC. Further studies might evaluate the clinical impact of cimetidine and amiloride in the treatment of HCC patients alone or in combination with other anti-tumoral agents.
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Fujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Kawase, Jin
Ozawa, Soj
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Fujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Ozawa, Soj
Kobayashi, Kenichi
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Fujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Kobayashi, Kenichi
Imaeda, Yoshihiro
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Fujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Imaeda, Yoshihiro
Umemoto, Shunji
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Fujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Umemoto, Shunji
Matsumoto, Sumio
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Natl Hosp Org Tokyo Med Ctr, Dept Surg, Meguro Ku, Tokyo 1528902, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
Matsumoto, Sumio
Ueda, Masakazu
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机构:
Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, JapanFujita Hlth Univ, Sch Med, Dept Gen & Gastrointestinal Surg, Nakagawa Ku, Aichi 4548509, Japan
机构:China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
Jiang, Cheng-Gang
Li, Jia-Bin
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机构:China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
Li, Jia-Bin
Liu, Fu-Rong
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机构:China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
Liu, Fu-Rong
Wu, Tao
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机构:China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
Wu, Tao
Yu, Miao
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机构:China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
Yu, Miao
Xu, Hui-Mian
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China Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Oncol, Shenyang 110001, Liaoning, Peoples R China
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China Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110001, Peoples R ChinaChina Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
Liu, Fu-Rong
Jiang, Cheng-Gang
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China Med Univ, Affiliated Hosp 1, Dept Surg Oncol, Shenyang 110001, Peoples R ChinaChina Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
Jiang, Cheng-Gang
Li, Yan-Shu
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China Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110001, Peoples R ChinaChina Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
Li, Yan-Shu
Li, Jia-Bin
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China Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110001, Peoples R ChinaChina Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
Li, Jia-Bin
Li, Feng
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China Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China
China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang 110001, Peoples R ChinaChina Med Univ, Dept Cell Biol, Key Lab Cell Biol, Minist Publ Hlth, Shenyang 110001, Peoples R China