J Korean Cancer Assoc.
1997 Feb;29(1):69-80.
Evaluation of Biologic Phenotype by Midkine Gene Expression in Gastric Cancer as a Target for Biotherapy
- Affiliations
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- 1Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
- 2Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, Korea.
- 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
- 4Department of General Surgery, Yonsei University College of Medicine, Seoul, Korea.
Abstract
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PURPOSE: We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor, midkine (MK) expression.
MATERIALS AND METHODS
Nine gastric cancer cell lines and 25 gastric cancer tissues were tested for MK expression by Northern blot analysis. Soft agar assay for in vitro tumorigenesis, cross- feeding assay for paracrine angiogenic activity, ELISA for uPA and PAI-1 measurement were performed.
RESULTS
MK expression was found in 67% (6/9) of the gastric cancer cell lines, and 56% (14/25) of the primary gastric cancer tissues. Gastric cancer cell lines with MK expression were more tumorigenic in soft agar assay and endothelial cell growth stimulatory in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity.
CONCLUSION
Gastric cancer cells with increased MK gene expression showed increased tumorigenic and angiogenic activity. Therefore, this proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer treatment.
Keyword
MeSH Terms
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Agar
Biological Therapy*
Blotting, Northern
Carcinogenesis
Cell Line
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Gene Expression*
Pentosan Sulfuric Polyester
Phenotype*
Plasminogen Activator Inhibitor 1
Stomach Neoplasms*
Urokinase-Type Plasminogen Activator
Agar
Pentosan Sulfuric Polyester
Plasminogen Activator Inhibitor 1
Urokinase-Type Plasminogen Activator
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