Experimental Study Of The Relationship Among The Expression Of Insulin-like Growth Factor-binding Protein 2,Invasive Progression Of Gastric Cancer And Peritoneal Metastasis Of Gastric Cancer

Insulin-like Growth Factor-binding Protein 2(IGFBP-2) is a member of six high-affinity IGF-binding proteins (IGFBP-1 to IGFBP-6) and may modulate the biological actions of IGFs in either a positive or negative way. Furthermore, IGF-independent cell effects of IGFBP-2 have been described, it is correlated with tumor cell growth, adhesion, invasion and tumor angiogenesis.IGFBP-2 mRNA was expressed in all gastric cancer cell lines, whereas else IGFBPs were expressed in portion of cell lines. IGFBP-2 mRNA was apparently down-regulated in gastric cancer cell lines with high potential for metastasis to the peritoneal cavity. These suggested that IGFBP-2 may be high correlated with gastric cancer and further studies are needed.Objective: To detect the expression of IGFBP-2 mRNA in gastric primary cancer tissues and metastasis tissues, in the mean time, detect theexpression of IGFBP-2 protein, in order to explore its roles in invasion, progression and peritoneal metastasis of gastric cancer.Methods: l.Collect the fresh tissues from normal gastric mucosae, primary gastric cancers, peritoneal metastases or peritoneal dissemination and lymph node metastases of 35 patients with gastric cancer during surgery operation, tissue fragments were divided into two portions and one portions were frozen in liquid nitrogen immediately and stored at -80°C until RNA extraction. 2.Another portions of samples were formalin-fixed and paraffin-embedded, they were sliced up and stained with hematoxylin-eosin for pathologyical examination. 3.The IGFBP-2 mRNA expression levels in the matching samples were determined by Quantitative Real-time RT-PCR. 4.The IGFBP-2 protein expression levels in the paraffin-embedded samples were measured by Immunohistochemistry and image analysis. 5 .The serum levels of tumor marker correlated with gastric cancer were detected before operation.Results: l.The levels of IGFBP-2 mRNA expression in gastric primary cancer tissues were significantly higher than those in normal gastric mucosae. IGFBP-2 mRNA expression levels showed no any differences among the tissues of normal gastric mucosae, peritoneal metastases and lymph node metastases (P>0.05). Yet, the significantly down-regulation was observed in the peritoneal metastases and lymph node metastases compared with primary tumors (P<0. 05). 2.The expressions of IGFBP-2 protein in gastric primary tumor tissues were significantly higher than those in normal gastric mucosae (P<0. 05). No statistical differences were observed among normal gastric mucosae, peritoneal metastases and lymph node metastases (P>0. 05). Theexpressions of IGFBP-2 protein showed significantly down-regulation in the peritoneal metastases and lymph node metastases compared with primary tumors (P<0. 05). 3. No differences were detected in the serum levels of tumor marker correlated with gastric cancer.Conclusions: 1. IGFBP-2 might be produced and secreted by gastric primary tumour cells, it promotes Invasion and Progression of gastric cancer in IGF-dependent or independent of IGF. 2. IGFBP-2 down-regulated expression enhances peritoneal metastasis and lymph node metastasis of gastric cancer. 3. IGFBP-2 expression levels are positively correlated with grade of gastric cancer, so it can become a grade marker. 4. IGFBP-2 might be a useful new method for clinical prognostication and treatment of gastric cancer and peritoneal metastasis.