Role of carbonic anhydrase in proliferation and invasion of gastrointestinal tumors.

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Among the carbonic anhydrase(CA) gene family, CA-related proteins(CA-RP) were investigated for the effect on proliferation and invasion properties of colon cancer, gastrointestinal stromal tumor(GIST), and also lung cancer.1.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured colon cancer cells (Lovo) increased proliferation and invasion properties compared to wild-type Lovo, which were shown by MTT assay and by using chemotaxis chambers.2.Xenograft produced by injection of ectopically CA-RP VIII-expressed Lovo into mice (6 weeks-old female, n=5) showed increased tumor growth rate compared to that of wild-type Lovo (p<0.05).3.Immunohistochemical analysis in GIST tissue specimens (n=26) showed positive staining for CA-RP VIII in 14 cases (54%), for CA-RP X in none and for CA-RP XI in 24 cases (92%). Otherwise, intestinal cell of Cajar that has been believed to develop to GIST showed no expression of all three CA-RPs.4.Ectopic expression of CA-RP XI by cDNA transfection in the cultured GIST cells (GIST-T1) increased proliferation and invasion properties compared to wild-type GIST-T1, which were shown by MTT assay and by using chemotaxis chambers.5.Immunohistochemical analysis for expression of CA-RP VIII showed weak staining in bronchial ciliated cells in normal lung. Otherwise, 75% of squamous cell carcinoma (n=24) and 68% of adenocarcinoma (n=25) showed strong expression of CA-RP VIII, especially in the marginal area of the tumors.6.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured lung cancer cells (PC9) increased proliferation property compared to wild-type PC9.These findings suggest CA-RPs VIII and XI function to enhance proliferation and invasion in gastrointestinal tumor cells. Similar results were observed in lung cancer cells, indicating that the finings is commonly observed during carcinogenesis.