1471

CST3

cystatin C;CST3;cystatin C

bA218C14.4 (cystatin C)|cystatin 3|cystatin-3|cystatin-C|gamma-trace|neuroendocrine basic polypeptide|post-gamma-globulin

20p11.21

protein-coding

AIMS AND BACKGROUND: Cystatin C is a member of the cysteine protease inhibitors and its function is to decrease protease activity. A recent study showed that it was aberrantly expressed in many malignant tumors in association with tumor invasion and metastasis. We attempted to detect its expression in esophageal cancer tissues and adjacent reparative normal tissues. METHODS AND DESIGN: Samples of cancers and non-cancerous esophageal tissues were obtained as matched pairs from 30 surgery patients with esophageal cancer and paraffin embedded. The expression of cystatin C in tissues was investigated by immunohistochemistry. Fisher's exact test was used to analyze the relationship between esophageal cancer tissues and adjacent normal tissues. Furthermore, mRNA was extracted, and reverse transcriptase polymerase chain reaction was performed. RESULTS: The intensity of cystatin C immunostaining in tumor tissues was increased compared to that of adjacent normal tissues. mRNA expression of the cystatin C gene was greater in esophageal cancer than in normal tissues (P <0.05). CONCLUSIONS: Our results indicate that cystatin C may play an important role in the pathogenesis and metastasis of esophageal cancer.

BACKGROUND: Cysteine proteases are involved in the extension of cancer into the subarachnoid space. The presence of cathepsins B and H along with their potent inhibitor cystatin C in the cerebrospinal fluid (CSF) was investigated in patients with leptomeningeal metastasis of cancer (LM). MATERIALS AND METHODS: CSF samples were obtained in 16 cases of LM (10 solid tumors and 6 leukemia or lymphoma) and compared with 11 cancer cases without involvement of the central nervous system, 12 multiple sclerosis cases and 34 healthy volunteers. The activity of the enzymes was measured, their molecular forms were analyzed by the Western blotting, and the concentration of cystatin C was measured by ELISA. Immunohistochemistry of the leptomeningeal tissues was also performed in six autopsy cases of LM. RESULTS: High activities of cathepsins B and H along with decreased cystatin C concentration were observed in CSF of LM as compared with three control groups. Western blot analysis revealed higher concentration of the enzyme protein as well as its active forms in samples with higher enzyme activity. Cells metastasizing leptomeningeal tissue were clearly positive in immunohistochemical staining of cathepsins, indicating active production by tumor cells. CONCLUSION: Production of cathepsins B and H by tumor cells and their high activity along with concomitant decrease of their potent inhibitor, cystatin C, in the CSF might contribute in the process of metastasis and spread of the cancer cells in the leptomeningeal tissues. A high enzyme activity/cystatin C concentration ratio in the CSF could be useful when diagnosing LM in combination with other parameters.