Abstract | BACKGROUND: METHODS: CTGF expression levels for wild-type and stable overexpression clones were determined by Western blotting and quantitative polymerase chain reaction (Q-PCR). Univariate and multivariate analyses, immunohistochemistry, and survival probability analyses were performed on gastric cancer patients. The extracellular matrix components involved in CTGF-regulated adhesion were determined. Recombinant CTGF was added to cells or coinoculated with gastric cancer cells into mice to evaluate its therapeutic potential. RESULTS: CTGF overexpression and treatment with the recombinant protein significantly inhibited cell adhesion. In vivo peritoneal metastasis demonstrated that CTGF-stable transfectants markedly decreased the number and size of tumor nodules in the mesentery. Statistical analysis of gastric cancer patient data showed that patients expressing higher CTGF levels had earlier TNM staging and a higher survival probability after the surgery. Integrin α3β1 was the cell adhesion molecule mediating gastric cancer cell adhesion to laminin, and blocking of integrin α3β1 prevented gastric cancer cell adhesion to recombinant CTGF. Coimmunoprecipitation results indicated that CTGF binds to integrin α3. Coinoculation of recombinant CTGF and gastric cancer cell lines in mice showed effective inhibition of peritoneal dissemination. CONCLUSIONS:
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Authors | Chiung-Nien Chen, Cheng-Chi Chang, Hong-Shiee Lai, Yung-Ming Jeng, Chia-I Chen, King-Jeng Chang, Po-Huang Lee, Hsinyu Lee |
Journal | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
(Gastric Cancer)
Vol. 18
Issue 3
Pg. 504-15
(Jul 2015)
ISSN: 1436-3305 [Electronic] Japan |
PMID | 24985492
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCN2 protein, human
- Integrin alpha3beta1
- Laminin
- Recombinant Proteins
- Connective Tissue Growth Factor
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Topics |
- Aged
- Animals
- Cell Adhesion
(drug effects)
- Connective Tissue Growth Factor
(genetics, metabolism, pharmacology)
- Female
- Humans
- Integrin alpha3beta1
(metabolism)
- Laminin
(metabolism)
- Male
- Mice, SCID
- Middle Aged
- Peritoneal Neoplasms
(metabolism, pathology, secondary)
- Recombinant Proteins
(genetics, pharmacology)
- Stomach Neoplasms
(metabolism, mortality, pathology, surgery)
- Tumor Cells, Cultured
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