Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma

Shinji Tanaka, Keishi Sugimachi, Toshifumi Kameyama, Shin ichiro Maehara, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Yoshihiko Maehara

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Abstract

Family members of the connective tissue growth factor, cysteine-rich 61, nephroblastoma over-expressed gene (CCN) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and tumor progression. In this study, we identified a CCN family member, WISP1v, as over-expressed in human cholangiocarcinomas. Genetic analysis of WISP1v was performed on surgically resected specimens of cholangiocarcinoma. The WISP1v biological effects were analyzed using the HuCCT1 human cholangiocarcinoma cell line. The WISP1v gene was expressed in 19 of 39 cholangiocarcinoma tissues (49%) but not in normal livers. Expression of WISP1v was significantly associated with lymphatic and perineural invasion of tumor cells (P < .05), as well as a poor clinical prognosis (P < .01). In the intraductal papillary cholangiocarcinomas, WISP1v was detected only in the cases with duct wall invasion but not in the cases without duct wall invasion (P < .05). No mutation of WISP1v gene was detected in the examined samples. In vitro analysis revealed that WISP1v stimulated the invasive phenotype of cholangiocarcinoma cells with activation of both p38 and p42/p44 mitogen-activated protein kinases (MAPKs). Furthermore, WISP1v-induced cholangiocarcinoma invasion was significantly suppressed by the p38 MAPK inhibitor SB203580 but not by the p42/p44 MAPK kinase (MEK) inhibitor PD98059. Our findings suggest that WISP1v-mediated signaling is involved in the generation of invasive cellular properties and leads to progression of cholangiocarcinoma.

Original languageEnglish
Pages (from-to)1122-1129
Number of pages8
JournalHepatology
Volume37
Issue number5
DOIs
Publication statusPublished - May 1 2003

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Cholangiocarcinoma
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Cysteine
Genes
Connective Tissue Growth Factor
Wilms Tumor
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Neoplasms
Phenotype
Cell Line
Mutation
Liver

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Tanaka, S., Sugimachi, K., Kameyama, T., Maehara, S. I., Shirabe, K., Shimada, M., ... Maehara, Y. (2003). Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. Hepatology, 37(5), 1122-1129. https://doi.org/10.1053/jhep.2003.50187

Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. / Tanaka, Shinji; Sugimachi, Keishi; Kameyama, Toshifumi; Maehara, Shin ichiro; Shirabe, Ken; Shimada, Mitsuo; Wands, Jack R.; Maehara, Yoshihiko.

In: Hepatology, Vol. 37, No. 5, 01.05.2003, p. 1122-1129.

Research output: Contribution to journalArticle

Tanaka, S, Sugimachi, K, Kameyama, T, Maehara, SI, Shirabe, K, Shimada, M, Wands, JR & Maehara, Y 2003, 'Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma', Hepatology, vol. 37, no. 5, pp. 1122-1129. https://doi.org/10.1053/jhep.2003.50187
Tanaka S, Sugimachi K, Kameyama T, Maehara SI, Shirabe K, Shimada M et al. Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. Hepatology. 2003 May 1;37(5):1122-1129. https://doi.org/10.1053/jhep.2003.50187
Tanaka, Shinji ; Sugimachi, Keishi ; Kameyama, Toshifumi ; Maehara, Shin ichiro ; Shirabe, Ken ; Shimada, Mitsuo ; Wands, Jack R. ; Maehara, Yoshihiko. / Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. In: Hepatology. 2003 ; Vol. 37, No. 5. pp. 1122-1129.
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