| Theme |
Diagnosis and Treatment of Scirrhous Gastric Cancer -- Current Status and Future Prospects |
| Title |
Mechanisms Responsible for Peritoneal Dissemination and Molecular Targeting |
| Author |
Masakazu Yashiro |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine / Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicin |
| Author |
Yuhiko Fuyuhiro |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine |
| Author |
Junko Matsuoka |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine |
| Author |
Tsuyoshi Hasegawa |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine |
| Author |
Satoru Noda |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine |
| Author |
Kosei Hirakawa |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine |
| [ Summary ] |
Scirrhous gastric carcinoma cells invade into the submucosa beyond the mucularis mucosae. MMP-2 production from fibroblasts and loss of cell-cell adhesion through down-regulation of E-cadherin and desmoglein-2 may be important for invasion by scirrhous cancer cells. TGFβ or HGF produced from stromal fibroblasts stimulate the invasive ability of scirrhous gastric cancer cells. Cancer cells free in the abdominal cavity initially adhere to hyaluronic acid on the mesothelial cells mediated by CD44 on the cancer cells. Thereafter, cancer cells adhere to the submesothelial matrix of laminin, fibronectin, and collagen through α2β1- and α3β1-integrin expressed by cancer cells. Gastric cancer cells leaving the primary tumor are exposed to low oxygen levels in the peritoneal cavity. Hypoxia increases the expression of integrin by cancer cells. Peritoneal fibroblasts are induced by cancer cells to morphologically evolve into mesothelial cells, and stimulate the migratory capability of cancer cells through the activity of TGFβ, HGF and MMPs. Peritoneal fibrosis induced by cancer cells prior to cancer metastases may create a congenial environmental "soil" for peritoneal metastases of scirrhous gastric carcinoma. TGFβR inhibitors decrease the expression of α2-, α3- and α5-integrin in cancer, resulting in decreased adhesive and invasive abilities for scirrhous gastric cancer cells into the peritoneum. |