Seprase, a Membrane-Type Serine Protease, Has Different Expression Patterns in Intestinal- and Diffuse-Type Gastric Cancer

Abstract

Objective: Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated. Methods: Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting. Results: Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer. Conclusion: These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.

Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma

“…Furthermore, this process degrades local extracellular matrix components that are required for cell migration and matrix invasion during tumor invasion, angiogenesis and metastasis (21). Previous studies have revealed that seprase overexpression was evident in stromal fibroblasts and tumor cells in invasive breast, gastric, colonic and cervical carcinomas; however, it was absent or undetectable in all normal tissue cells, with the exception of cells involved in the early stages of wound healing (22)(23)(24)(25). In addition, an in vivo study using a mouse model of human breast cancer, demonstrated that seprase increased microvessel density and promoted rapid tumor growth (26).…”

Seprase Promotes Rapid Tumor Growth and Increased Microvessel Density in a Mouse Model of Human Breast Cancer

“…We investigated 27 cases of infiltrating ductal carcinoma of the breast and found that the carcinoma cells as well as the stromal cells express seprase (2). The finding of carcinoma cell expression of seprase is supported by the constitutive expression of seprase in several human breast cancer cell lines and by its expression in the malignant cells of a number of other carcinomas including melanoma and gastric cancer (11,14,30). On the other hand, two other studies of human breast cancer, including one survey of 112 cases, have indicated that seprase is detected primarily in the reactive stromal fibroblasts, suggesting that reactive fibroblasts are the main source of seprase in breast cancer (21,29).…”

Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers

“…Similar pattern of expression has been reported in esophageal adenocarcinoma where FAP expression was observed in >98% of the cases in epithelial carcinoma cells. 62 FAP has also been reported to be overexpressed in epithelial as well as adjacent stromal cells in other cancers including diffuse-type of gastric cancer, 63 colorectal cancer 64 and gastric carcinoma. 65 …”