Connective Tissue Growth Factor Inhibits Metastasis and Acts as an Independent Prognostic Marker in Colorectal Cancer
Resource
GASTROENTEROLOGY 128(1), 9-23
Journal
GASTROENTEROLOGY 128(1)
Pages
9-23
Date Issued
2005-07-31
Date
2005-07-31
Author(s)
Lin, Been-Ren
DOI
932314B002261
Abstract
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 -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 -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.
SDGs
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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