| 共同演者 |
Imai Katsunori（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Hayashi Hiromitsu（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Hashimoto Daisuke（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Ikuta Yoshiaki（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Chikamoto Akira（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Beppu Toru（Department of Gastroenterological Surgery, Kumamoto University, Japan）, Imamura Takahisa（Department of Molecular Pathology, Kumamoto University, Japan）, Baba Hideo（Department of Gastroenterological Surgery, Kumamoto University, Japan） |
| 抄録 |
The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor（C5aR）and plays a crucial role in inflammation and immune reactions. There is emerging evidence that C5a is also generated in the cancer microenvironment, however, its direct influence on cancer cells has not been fully studied. Here, we show that C5aR was aberrantly expressed in a wide variety of human cancers and several cancer cell lines. C5a triggered cytoskeletal rearrangement of cancer cells in a C5aR-dependent manner. Time-lapse analysis and Matrigel chamber assay revealed that C5a enhances cell motility and invasiveness of C5aR-overexpressing cancer cells. C5a increased the release of matrix metalloproteinases（MMPs）from cancer cells by 2 to 11-fold, and inhibition of MMP activity abolished the C5a enhancing effect on cancer cell invasion. When C5aR-overexpressing cells treated with C5a were injected via tail vein into nude mouse, the incidence of micrometastasis in lungs was higher than non-treated C5aR-overexpressing cells and control cells. These results illustrate a novel activity of C5a-C5aR axis that promotes cancer cell invasion and metastasis through cytoskeletal rearrangement and MMP release. Thus, targeting this signaling pathway may provide a useful therapeutic option for cancer treatment. |
