Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients
Open Access
- 17 July 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 97 (3), 398-404
- https://doi.org/10.1038/sj.bjc.6603877
Abstract
Transforming growth factor-β1 (TGF-β1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-β1 activation and localisation of TGF-β1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-β1 staining by immunohistochemistry. Active TGF-β1 was present in malignant epithelial cells, but most strongly in smooth muscle actin expressing fibroblasts. Normal gastric mucosa from the same patient showed some staining for total, and little for active TGF-β1. Active TGF-β1 levels were determined by ELISA on tissue homogenates, confirming a strong increase in active TGF-β1 in tumours compared to corresponding normal mucosa. Moreover, high tumour TGF-β1 activity levels were significantly associated with clinical parameters, including worse survival of the patients. Total and active TGF-β1 levels were not correlated, suggesting a specific activation process. Of the different proteases tested, active TGF-β1 levels were only correlated with urokinase activity levels. The correlation with urokinase activity suggests a role for plasmin in TGF-β1 activation in the tumour microenvironment, resulting in transformation of resident fibroblasts to tumour promoting myofibroblasts. In conclusion we have shown localisation and clinical relevance of TGF-β1 activity levels in gastric cancer.Keywords
This publication has 45 references indexed in Scilit:
- Matrix Metalloproteinase 2 Activation of Transforming Growth Factor-β1 (TGF-β1) and TGF-β1–Type II Receptor Signaling Within the Aged Arterial WallArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Increased Expression of Integrin αvβ5 Induces the Myofibroblastic Differentiation of Dermal FibroblastsThe American Journal of Pathology, 2006
- Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF‐beta 1 secreted by the tumor cellsJournal of Cellular Biochemistry, 2005
- Transforming Growth Factor-β Is Activated by Plasmin and Inhibits Smooth Muscle Cell Death in Human Saphenous VeinJournal of Vascular Research, 2005
- Expression of truncated latent TGF-β-binding protein modulates TGF-β signalingJournal of Cell Science, 2005
- Role of Transforming Growth Factor Beta in Human CancerJournal of Clinical Oncology, 2005
- TGF-β signaling in cancer – a double-edged swordTrends in Cell Biology, 2001
- Authentic Matrix Vesicles Contain Active Metalloproteases (MMP)Published by Elsevier BV ,2001
- The L45 loop in type I receptors for TGF‐β family members is a critical determinant in specifying Smad isoform activationFEBS Letters, 1998
- Urokinase receptor and colorectal cancer survivalThe Lancet, 1994