Impacts of Cancer-Associated Stromal Cells on Growth of Human Gastric Cancer Cell Lines

Abstract

Scirrhous gastric cancer (SGC) is highly resistant to treatment and has a poor prognosis. Tumor stromal cells are considered to play vital roles in the development of SGC. However, interactions between cancer cells and stromal cells are poorly understood. We evaluated the importance of direct contact between cancer cells and stromal cells in vitro . We obtained gastric cancer-associated stromal cells (GCSCs) and normal gastric stromal cells (GSCs) from six patients. We co-cultured these cells with MKN45 solid-type gastric cancer and HSC43 SGC cells, respectively, for 7 days. Both gastric cancer cell lines were labeled with fluorescent protein to distinguish them from stromal cells in culture. We used two co-culture models: direct contact (GCSCs and GSCs), in which cancer cells and stromal cells were mixed, and indirect contact (GCSCs only), in which cells were separated by cell culture inserts. We also compared the gene expression profiles of GCSCs and GSCs by microarray assays. The cell growth rate was significantly higher in the direct-contact GCSC model compared with that in monocultured cells in MKN45, but not in HSC43 cells. For either cell line, there was no significant difference in growth rates between indirect GCSC co-cultures and monocultures, and no difference between direct or indirect GSC co-cultures and monocultures. In terms of gene expression, fibroblast growth factor 9, which has an anti-apoptotic effect on gastric cancer cells, was more up-regulated in GCSCs than in GSCs. Flow cytometry revealed no difference between GCSCs and GSCs in terms of marker expression. In conclusion, although stromal cells can influence the growth of gastric cancer cells, our results suggest that the impacts of interactions with stromal cells might vary according to the specific characteristics of the cancer cells.