The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal Metastasis of Gastric Cancer (CTGF)

June 22, 2012 updated by: National Taiwan University Hospital

For the past 50 years, gastric cancer has been one of the ten most frequent cancers and the second leading cause of cancer-related death in the world. In Taiwan, it is the fifth most common cause of cancer-related deaths, accounting for 6.3% of all cancer deaths. The poor prognosis of gastric cancer is mostly caused by the extensive metastasis to the lymph nodes, liver, and peritoneal dissemination even if curative resection was performed. The main cause of recurrence after curative or noncurative resection of advanced tumors is peritoneal metastasis because of possible direct spillage and dissemination of tumor cells as a result of surgical manipulation, and it is associated with a poor prognosis. As yet, no effective treatment has been developed for this condition. The development of peritoneal metastasis is a multistep process, beginning with attachment to peritoneal mesothelial cells, retraction of the mesothelial cells and exposure of the basement membrane, attachment to the basement membrane, degradation in the extracellular matrix, proliferation by the cancer cells, and angiogenesis, and it is clear that many types of agents are involved at the various stages of this process. Developing a new therapeutic method for this mode of metastasis is very important for improvement of gastric cancer treatment.

CTGF is a secretory protein belonging to the CCN family (one among the three originally discovered members: cysteine-rich61, CTGF, and nephroblastoma-overexpressed gene). It is a multifunctional growth factor involved in wound healing, inflammation, cell adhesion, chemotaxis, apoptosis, tumor growth, and fibrosis. Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF overexpression was less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a better prognostic factor. These studies suggest that CTGF may involve the processes of peritoneal metastasis which includes cancer cell adhesion in peritoneum, proliferation and angiogenesis. Peritoneal mesothelium is the first surface encountered by disseminated tumor cells and successful adhesion is, therefore, of paramount importance in metastasis formation. Therefore, we hypothesized that CTGF is a potential molecule target, which may be related to cell adhesion to peritoneum, the first step of peritoneal metastasis, and its exact mechanism may includes proliferation and angiogenesis.

In order to answer these important questions, first, we have performed the preliminary studies to prove CTGF did express in different gastric cancer cell lines including AGS, N87, TSGH, and MKN-45 by using RT-PCR and Western blotting, and gastric cancer tissues by using immunohistochemical method. Second, we demonstrated different levels of CTGF expression in different cell lines pose different adhesion ability in in-vitro adhesion assay. Third, we conducted a transient CTGF-overexpressed MKN45 gastric cancer cell line, and CTGF-overexpressed cell line had lower adhesive ability compared to the control.

Next step in this project, we will be studying the roles of CTGF plays in cellular and molecular biology in vitro and in vivo and clinical significance associated with therapeutic potential of peritoneal metastasis from gastric cancer. We will generate stable clones of MKN45 cells harboring CTGF and its control cell line to elucidate the roles of CTGF in cancer cell adhesion, proliferation and angiogenesis in peritoneum.

Study Overview

Status

Unknown

Conditions

Study Type

Observational

Enrollment (Anticipated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Chiung-Nien Chen, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Gastric cancer patients Age 25-90

Description

Inclusion Criteria:

  • Gastric cancer patients who are elegible for curative surgery
  • Age 25-90

Exclusion Criteria:

  • Gastric cancer patients who are not elegible for curative surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Gastric cancer patients
Gastric cancer patients who receive curative surgery at National Taiwan University Hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To measure the expression level of CTGF in patient blood and tissue
Time Frame: 1 day
To determine the level of CTGF expression in gastric cancer patient specimens collected during surgery.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the survival probability of gastric cancer patients after surgery
Time Frame: 10 years from date of surgery
To determine the survival probability of gastric cancer patients after surgery
10 years from date of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Chiung-Nien Chen, MD, PhD, NTUH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (ANTICIPATED)

June 1, 2012

Study Completion (ANTICIPATED)

June 1, 2012

Study Registration Dates

First Submitted

June 21, 2012

First Submitted That Met QC Criteria

June 22, 2012

First Posted (ESTIMATE)

June 25, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

June 25, 2012

Last Update Submitted That Met QC Criteria

June 22, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200906054R

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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