Title
Active TGF-β1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence
Author
Hawinkels, L.J.A.C.
Verspaget, H.W.
van der Reijden, J.J.
van der Zon, J.M.
Verheijen, J.H.
Hommes, D.W.
Lamers, C.B.H.W.
Sier, C.F.M.
TNO Kwaliteit van Leven
Publication year
2009
Abstract
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.
Subject
Biology
Biomedical Research
actin
desmin
keratin
plasminogen activator inhibitor 1
Smad2 protein
SMAD2 protein, human
transforming growth factor beta1
tumor marker
urokinase
vimentin
adenoma
article
carcinoma
cell strain HT29
colorectal tumor
enzyme linked immunosorbent assay
female
fibroblast
human
immunohistochemistry
male
metabolism
pathology
reproducibility
sensitivity and specificity
smooth muscle
Actins
Adenoma
Carcinoma
Colorectal Neoplasms
Desmin
Enzyme-Linked Immunosorbent Assay
Female
Fibroblasts
HT29 Cells
Humans
Immunohistochemistry
Keratins
Male
Muscle, Smooth
Plasminogen Activator Inhibitor 1
Reproducibility of Results
Sensitivity and Specificity
Smad2 Protein
Transforming Growth Factor beta1
Tumor Markers, Biological
Urokinase-Type Plasminogen Activator
Vimentin
To reference this document use:
http://resolver.tudelft.nl/uuid:7d07ade7-d02b-4d85-8361-6f15bd70cd77
DOI
https://doi.org/10.1111/j.1349-7006.2009.01100.x
TNO identifier
241703
ISSN
1347-9032
Source
Cancer Science, 100 (4), 663-670
Document type
article