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In vitro and In vivo Evidence of Metallopanstimulin-1 in Gastric Cancer Progression and Tumorigenicity

Authors' Affiliation: Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China

Requests for reprints: Zheng-gang Zhu, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, People's Republic of China. Phone: 86-21-6467-4654; Fax: 86-21-6437-3909; E-mail: zhenggang_zhurj{at}yahoo.com.cn.

Purpose: The metallopanstimulin-1 (MPS-1) gene is a growth factor–inducible gene, which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy. However, it is unclear whether MPS-1 plays any role in gastric cancer development or progression. Our studies were designed to clarify the MPS-1 expression pattern and to explore its potential role in gastric cancer.

Experimental Design: The expression pattern of MPS-1 was determined in primary gastric cancer specimens and gastric cancer cell lines via immunohistochemistry and Western blotting. To investigate the functional significance of MPS-1 expression, three small interfering RNA (siRNA) expression plasmids were constructed and transfected into gastric cancer cell line SGC7901. The stable cell lines transfected with the siRNA targeting MPS-1 mRNA plasmids were selected and the biological features of these cells were examined.

Results: MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells. In addition, MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage, and was significantly higher in the late stage (P < 0.01). The MPS-1 expression level was significantly decreased in the transfected cells with MPS-1-specific siRNA expression plasmid pRNAT-133. Furthermore, the stable transfected cancer cells exhibited an increase in the incidence of spontaneous apoptosis and a decrease in growth ability and tumorigenicity in nude mice.

Conclusions: These results provide strong evidence that MPS-1 plays an important role in gastric cancer cell proliferation and development, and suggests that MPS-1 is a promising target for gastric cancer treatment.

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