Release of TGFssig-h3 by gastric myofibroblasts slows tumor growth and is decreased with cancer progression
Tumor progression has been linked to changes in the stromal environment. Myofibroblasts are stromal cells that are often increased in tumors but their contribution to cancer progression is not well understood. Here, we show that the secretomes of myofibroblasts derived from gastric cancers (CAMs...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2012
|
| Sorozat: | CARCINOGENESIS
33 No. 8 |
| doi: | 10.1093/carcin/bgs180 |
| mtmt: | 2000561 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/18758 |
| Tartalmi kivonat: | Tumor progression has been linked to changes in the stromal environment. Myofibroblasts are stromal cells that are often increased in tumors but their contribution to cancer progression is not well understood. Here, we show that the secretomes of myofibroblasts derived from gastric cancers (CAMs) differ in a functionally significant manner from those derived from adjacent tissue (ATMs). CAMs showed increased rates of migration and proliferation compared to ATMs or normal tissue myofibroblasts (NTMs). Moreover, conditioned medium (CM) from CAMs significantly stimulated migration, invasion and proliferation of gastric cancer cells compared with CM from ATMs or NTMs. Proteomic analysis of myofibroblast secretomes revealed decreased abundance of the extracellular matrix (ECM) adaptor protein TGFssig-h3 in CAMs, that was correlated with lymph node involvement and shorter survival. TGFssig-h3 inhibited IGF-II stimulated migration and proliferation of both cancer cells and myofibroblasts, and suppressed IGF-II activation of p42/44 MAPkinase; TGFssig-h3 knockdown increased IGF-II and CM- stimulated migration. Furthermore, administration of TGFssig-h3 inhibited myofibroblast-stimulated growth of gastric cancer xenografts. We conclude that stromal cells exert inhibitory as well as stimulatory effects on tumor cells; TGFssig-h3 is a stromal inhibitory factor that is decreased with progression of gastric cancers. |
|---|---|
| Terjedelem/Fizikai jellemzők: | 1553-1562 |
| ISSN: | 0143-3334 |