Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer

Been Ren Lin, Cheng Chi Chang, Ting Fang Che, Szu Ta Chen, Robert Jeen Chen Chen, Ching Yao Yang, Yung Ming Jeng, Jin Tung Liang, Po Huang Lee, King Jen Chang, Yat Pang Chau, Min Liang Kuo

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. The aim of this study was to investigate the role of CTGF in progression of colorectal cancer (CRC). Methods: Immunohistochemical staining of specimens from 119 patients with CRC was performed. Liposome-mediated transfection was used to introduce a CTGF expression vector into CRC cell lines. Transfectants were tested in invasive ability and experimental hepatic metastasis in BALB/c mice. Furthermore, a FOPflash/TOPflash reporter assay was performed to investigate CTGF on the β-catenin/T-cell factor signaling pathway. Results: Patients with stage II and stage III CRC whose tumors displayed high CTGF expression had a significantly higher overall survival and a disease-free advantage over patients with CRC with low CTGF expression. Alterations in the CTGF level in CRC cell lines modulated their invasive ability with an inverse correlation. In addition, a reduction in the CTGF level of CT26 cells after stable transfection with antisense CTGF resulted in increased liver metastasis in BALB/c mice. The activity of the β-catenin/T-cell factor signaling pathway and its downstream effector gene matrix metalloproteinase 7 in these CTGF-transfected cells was strongly attenuated. Blockage of matrix metalloproteinase 7 with its neutralizing antibodies inhibited increased invasiveness in antisense CTGF-transfected CT26 cells. Conclusions: Our results implicate CTGF as a key regulator of CRC invasion and metastasis, and it appears to be a useful and better prognosis factor for patients with stage II and stage III CRC.

Original languageEnglish
Pages (from-to)9-23
Number of pages15
JournalGastroenterology
Volume128
Issue number1
DOIs
Publication statusPublished - Jan 1 2005
Externally publishedYes

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Connective Tissue Growth Factor
Colorectal Neoplasms
Neoplasm Metastasis
Matrix Metalloproteinase 7
TCF Transcription Factors
Catenins
Transfection
Cell Line
Liver
Neutralizing Antibodies
Liposomes
Disease-Free Survival
Neoplasms

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lin, B. R., Chang, C. C., Che, T. F., Chen, S. T., Chen, R. J. C., Yang, C. Y., ... Kuo, M. L. (2005). Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer. Gastroenterology, 128(1), 9-23. https://doi.org/10.1053/j.gastro.2004.10.007

Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer. / Lin, Been Ren; Chang, Cheng Chi; Che, Ting Fang; Chen, Szu Ta; Chen, Robert Jeen Chen; Yang, Ching Yao; Jeng, Yung Ming; Liang, Jin Tung; Lee, Po Huang; Chang, King Jen; Chau, Yat Pang; Kuo, Min Liang.

In: Gastroenterology, Vol. 128, No. 1, 01.01.2005, p. 9-23.

Research output: Contribution to journalArticle

Lin, BR, Chang, CC, Che, TF, Chen, ST, Chen, RJC, Yang, CY, Jeng, YM, Liang, JT, Lee, PH, Chang, KJ, Chau, YP & Kuo, ML 2005, 'Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer', Gastroenterology, vol. 128, no. 1, pp. 9-23. https://doi.org/10.1053/j.gastro.2004.10.007
Lin, Been Ren ; Chang, Cheng Chi ; Che, Ting Fang ; Chen, Szu Ta ; Chen, Robert Jeen Chen ; Yang, Ching Yao ; Jeng, Yung Ming ; Liang, Jin Tung ; Lee, Po Huang ; Chang, King Jen ; Chau, Yat Pang ; Kuo, Min Liang. / Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer. In: Gastroenterology. 2005 ; Vol. 128, No. 1. pp. 9-23.
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abstract = "Background & Aims: Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. The aim of this study was to investigate the role of CTGF in progression of colorectal cancer (CRC). Methods: Immunohistochemical staining of specimens from 119 patients with CRC was performed. Liposome-mediated transfection was used to introduce a CTGF expression vector into CRC cell lines. Transfectants were tested in invasive ability and experimental hepatic metastasis in BALB/c mice. Furthermore, a FOPflash/TOPflash reporter assay was performed to investigate CTGF on the β-catenin/T-cell factor signaling pathway. Results: Patients with stage II and stage III CRC whose tumors displayed high CTGF expression had a significantly higher overall survival and a disease-free advantage over patients with CRC with low CTGF expression. Alterations in the CTGF level in CRC cell lines modulated their invasive ability with an inverse correlation. In addition, a reduction in the CTGF level of CT26 cells after stable transfection with antisense CTGF resulted in increased liver metastasis in BALB/c mice. The activity of the β-catenin/T-cell factor signaling pathway and its downstream effector gene matrix metalloproteinase 7 in these CTGF-transfected cells was strongly attenuated. Blockage of matrix metalloproteinase 7 with its neutralizing antibodies inhibited increased invasiveness in antisense CTGF-transfected CT26 cells. Conclusions: Our results implicate CTGF as a key regulator of CRC invasion and metastasis, and it appears to be a useful and better prognosis factor for patients with stage II and stage III CRC.",
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AU - Chen, Robert Jeen Chen

AU - Yang, Ching Yao

AU - Jeng, Yung Ming

AU - Liang, Jin Tung

AU - Lee, Po Huang

AU - Chang, King Jen

AU - Chau, Yat Pang

AU - Kuo, Min Liang

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