Enhancement of Metastatic and Invasive Capacity of Gastric Cancer Cells by Transforming Growth Factor-β1

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: gastric cancer transforming growth factor-β invasion metastasis
• 年，卷（期）: 2006,（3）
• 页码范围: 179-186
• 页数: 8页
• 语种: 英文

摘要

Transforming growth factor-β (TGF-β), a multifunctional cytokine, exerts contradictory roles in different kinds of cells. A number of studies have revealed its involvement in the progression of many types of tumors. To investigate the effect of TGF-β on gastric carcinoma, SGC7901, BGC823 and MKN28 (a TGF-β-resistant cell line) adenocarcinoma clones were used. After pretreatment in serum-free medium with or without 10 ng/ml TGF-β1, their experimental metastatic potential, chemotaxis, and invasive and adhesive ability were measured. Furthermore, zymography for gelatinase was processed. Liver colonies were also measured 4 weeks after inoculation of SGC7901, BGC823 and MKN28 in Balb/c nude mice, and an increase in the number of surface liver metastases was seen in SGC7901 (from 11.0±3.0 to 53.3±3.3) and BGC823(from 9.3±2.5 to 60.0±2.8) groups, whereas there was no difference between MKN28 groups (from 35.2±3.8 to 38.5±2.7 ). In vitro experiments showed that TGF-β1 increased the adhesion capacity of SGC7901and BGC823 cells to immobilized reconstituted basement membrane/fibronectin matrices and promoted their penetration through reconstituted basement membrane barriers. Zymography demonstrated that enhanced invasive potential was partly due to the increased type IV collagenolytic (gelatinolytic) activity, but there was no difference in type IV collagenolytic activity and other biological behaviors between MKN28 groups. These results suggested that TGF-β1 might modulate the metastatic potential of gastric cancer cells by promoting their ability to break down and penetrate basement membrane barriers and their adhesive and motile activities.We speculated that TGF-β1 might act as a progression-enhancing factor in gastric cancer. Therefore blockage of TGF-β or TGF-β signaling might prevent gastric cancer cells from invading and metastasizing.