Active TGF-β1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence

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Hawinkels, L.J.A.C.

Verspaget, H.W.

Reijden, J.J. van der

Zon, J.M. van der

Verheijen, J.H.

Hommes, D.W.

Lamers, C.B.H.W.

Sier, C.F.M.
Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a stepwise increase in the mucosa-adenoma-carcinoma sequence, active TGF-β1 levels are increased only in carcinomas but not in premalignant adenomas. Furthermore, solely active TGF-β1 levels are associated with the stage of the carcinomas and worse patient prognosis. Active TGF-β1 levels correlated significantly with plasminogen activator inhibitor (PAI)-1, α-smooth muscle actin (SMA) and several matrix-remodeling proteinases. Interestingly, SMA levels are also significantly increased in colorectal carcinomas but not in adenomas, suggesting that despite the enhanced total TGF-β1 levels, myofibroblast accumulation is not (yet) occurring in these premalignant neoplasias. The correlation between active TGF-β1 and SMA expression in tumors indicates that tumor-promoting myofibroblasts might arise as a result of increased TGF-β1 activation. These data underline the significance of the interaction between malignant cells and (myo)-fibroblasts in the tumor microenvironment, modulating the biologic behavior of colorectal cancer. © 2009 Japanese Cancer Association.
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Biomedical Researchactindesminkeratinplasminogen activator inhibitor 1Smad2 proteinSMAD2 protein, humantransforming growth factor beta1tumor markerurokinasevimentinadenomaarticlecarcinomacell strain HT29colorectal tumorenzyme linked immunosorbent assayfemalefibroblasthumanimmunohistochemistrymalemetabolismpathologyreproducibilitysensitivity and specificitysmooth muscleActinsAdenomaCarcinomaColorectal NeoplasmsDesminEnzyme-Linked Immunosorbent AssayFemaleFibroblastsHT29 CellsHumansImmunohistochemistryKeratinsMaleMuscle, SmoothPlasminogen Activator Inhibitor 1Reproducibility of ResultsSensitivity and SpecificitySmad2 ProteinTransforming Growth Factor beta1Tumor Markers, BiologicalUrokinase-Type Plasminogen ActivatorVimentin
TNO Identifier
241703
Repository link
https://resolver.tno.nl/uuid:7d07ade7-d02b-4d85-8361-6f15bd70cd77
ISSN
13479032
Source
Cancer Science, 100(4), pp. 663-670.
Pages
663-670
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