High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma

Shinichi Aishima, Yuji Basaki, Yoshinao Oda, Yohsuke Kuroda, Yunosuke Nishihara, Kenichi Taguchi, Akinobu Taketomi, Yoshihiko Maehara, Fumihito Hosoi, Yuichiro Maruyama, Abbas Fotovati, Shinji Oie, Mayumi Ono, Takato Ueno, Michio Sata, Hirohisa Yano, Masamichi Kojiro, Michihiko Kuwano, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

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Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) modulates cell proliferation of various cancer cell types. However, it remains unclear how IGF-IGFBP-3-signaling is involved in growth and progression of hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP-3 in HCC. Type 1 receptor for IGF (IGF-1R) was expressed at various levels in the seven lines examined, but IGF-2R was not expressed. Of the seven lines, the growth of HAK-1B, KIM-1, KYN-2 and HepG2 cells was stimulated in a dose-dependent manner by the exogenous addition of IGF-I or IGF-II, but the HAK-1A, KYN-1 and KYN-3 cell lines showed no growth. Exogenous addition of IGFBP-3 markedly blocked IGF-I and IGF-II-stimulated cell growth of KYN-2 and HepG2 cells, and moderately stimulated that of KIM-1 and HAK-1B cells, but no growth of the KYN-1, KYN-3 and HAK-1A cell lines was observed. IGF-I enhanced the phosphorylation of IGF-1R, Akt and Erk1/2 in KYN-2 cells, and coadministration of IGFBP-3 blocked all types of activation by IGF-I investigated here. In contrast, no such activation by IGF-I was detected in KYN-3 cells. IGFBP-3 also suppressed IGF-I-induced cell invasion by KYN-2 cells. Moreover, we were able to observe the apparent expression of IGFBP-3 in KYN-3 cells, but not in the other six cell lines. Furthermore reduced expression of IGFBP-3, but not that of IGF-1R, was significantly correlated with tumor size, histological differentiation, capsular invasion and portal venous invasion. Low expression of IGFBP-3 was independently associated with poor survival. IGFBP-3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC.

Original languageEnglish
Pages (from-to)1182-1190
Number of pages9
JournalCancer Science
Volume97
Issue number11
DOIs
Publication statusPublished - Nov 1 2006

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Insulin-Like Growth Factor Binding Protein 3
Hepatocellular Carcinoma
Insulin-Like Growth Factor I
Growth
Insulin-Like Growth Factor II
Hep G2 Cells
Cell Line
IGF Type 1 Receptor
Neoplasms
Phosphorylation
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma. / Aishima, Shinichi; Basaki, Yuji; Oda, Yoshinao; Kuroda, Yohsuke; Nishihara, Yunosuke; Taguchi, Kenichi; Taketomi, Akinobu; Maehara, Yoshihiko; Hosoi, Fumihito; Maruyama, Yuichiro; Fotovati, Abbas; Oie, Shinji; Ono, Mayumi; Ueno, Takato; Sata, Michio; Yano, Hirohisa; Kojiro, Masamichi; Kuwano, Michihiko; Tsuneyoshi, Masazumi.

In: Cancer Science, Vol. 97, No. 11, 01.11.2006, p. 1182-1190.

Research output: Contribution to journalArticle

Aishima, S, Basaki, Y, Oda, Y, Kuroda, Y, Nishihara, Y, Taguchi, K, Taketomi, A, Maehara, Y, Hosoi, F, Maruyama, Y, Fotovati, A, Oie, S, Ono, M, Ueno, T, Sata, M, Yano, H, Kojiro, M, Kuwano, M & Tsuneyoshi, M 2006, 'High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma', Cancer Science, vol. 97, no. 11, pp. 1182-1190. https://doi.org/10.1111/j.1349-7006.2006.00322.x
Aishima, Shinichi ; Basaki, Yuji ; Oda, Yoshinao ; Kuroda, Yohsuke ; Nishihara, Yunosuke ; Taguchi, Kenichi ; Taketomi, Akinobu ; Maehara, Yoshihiko ; Hosoi, Fumihito ; Maruyama, Yuichiro ; Fotovati, Abbas ; Oie, Shinji ; Ono, Mayumi ; Ueno, Takato ; Sata, Michio ; Yano, Hirohisa ; Kojiro, Masamichi ; Kuwano, Michihiko ; Tsuneyoshi, Masazumi. / High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma. In: Cancer Science. 2006 ; Vol. 97, No. 11. pp. 1182-1190.
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AU - Nishihara, Yunosuke

AU - Taguchi, Kenichi

AU - Taketomi, Akinobu

AU - Maehara, Yoshihiko

AU - Hosoi, Fumihito

AU - Maruyama, Yuichiro

AU - Fotovati, Abbas

AU - Oie, Shinji

AU - Ono, Mayumi

AU - Ueno, Takato

AU - Sata, Michio

AU - Yano, Hirohisa

AU - Kojiro, Masamichi

AU - Kuwano, Michihiko

AU - Tsuneyoshi, Masazumi

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N2 - Insulin-like growth factor binding protein-3 (IGFBP-3) modulates cell proliferation of various cancer cell types. However, it remains unclear how IGF-IGFBP-3-signaling is involved in growth and progression of hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the role of IGFBP-3 in HCC. Type 1 receptor for IGF (IGF-1R) was expressed at various levels in the seven lines examined, but IGF-2R was not expressed. Of the seven lines, the growth of HAK-1B, KIM-1, KYN-2 and HepG2 cells was stimulated in a dose-dependent manner by the exogenous addition of IGF-I or IGF-II, but the HAK-1A, KYN-1 and KYN-3 cell lines showed no growth. Exogenous addition of IGFBP-3 markedly blocked IGF-I and IGF-II-stimulated cell growth of KYN-2 and HepG2 cells, and moderately stimulated that of KIM-1 and HAK-1B cells, but no growth of the KYN-1, KYN-3 and HAK-1A cell lines was observed. IGF-I enhanced the phosphorylation of IGF-1R, Akt and Erk1/2 in KYN-2 cells, and coadministration of IGFBP-3 blocked all types of activation by IGF-I investigated here. In contrast, no such activation by IGF-I was detected in KYN-3 cells. IGFBP-3 also suppressed IGF-I-induced cell invasion by KYN-2 cells. Moreover, we were able to observe the apparent expression of IGFBP-3 in KYN-3 cells, but not in the other six cell lines. Furthermore reduced expression of IGFBP-3, but not that of IGF-1R, was significantly correlated with tumor size, histological differentiation, capsular invasion and portal venous invasion. Low expression of IGFBP-3 was independently associated with poor survival. IGFBP-3 could be a molecular target of intrinsic importance for further development of novel therapeutic strategy against HCC.

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