Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer

Been Ren Lin, Cheng Chi Chang, Robert Jeen Chen Chen, Yung Ming Jeng, Jin Tung Liang, Po Huang Lee, King Jen Chang, Min Liang Kuo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. Experimental Design: A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. Results: The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. Conclusions: CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients.

Original languageEnglish
Pages (from-to)3077-3088
Number of pages12
JournalClinical Cancer Research
Volume17
Issue number10
DOIs
Publication statusPublished - May 15 2011
Externally publishedYes

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Connective Tissue Growth Factor
Colorectal Neoplasms
Carcinoma
Therapeutics
Cell Adhesion
Integrins
Neoplasms
Chemoprevention
Intraperitoneal Injections
Reverse Transcriptase Polymerase Chain Reaction
Transfection

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer. / Lin, Been Ren; Chang, Cheng Chi; Chen, Robert Jeen Chen; Jeng, Yung Ming; Liang, Jin Tung; Lee, Po Huang; Chang, King Jen; Kuo, Min Liang.

In: Clinical Cancer Research, Vol. 17, No. 10, 15.05.2011, p. 3077-3088.

Research output: Contribution to journalArticle

Lin, Been Ren ; Chang, Cheng Chi ; Chen, Robert Jeen Chen ; Jeng, Yung Ming ; Liang, Jin Tung ; Lee, Po Huang ; Chang, King Jen ; Kuo, Min Liang. / Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 10. pp. 3077-3088.
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abstract = "Purpose: Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. Experimental Design: A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. Results: The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. Conclusions: CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients.",
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