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Published in: International Journal of Colorectal Disease 5/2010

01-05-2010 | Original Article

Role of TGF-β1, its receptor TGFβRII, and Smad proteins in the progression of colorectal cancer

Authors: Maya Gulubova, Irena Manolova, Julian Ananiev, Alexander Julianov, Yovcho Yovchev, Katya Peeva

Published in: International Journal of Colorectal Disease | Issue 5/2010

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Abstract

Aim

In the current study, we investigated the expression of TGF-β1, its receptor TGFβRII, and the signaling proteins Smad4 and Smad7 in colorectal cancer tissue in relation to infiltration with antigen-presenting cells and some clinical and pathologic parameters of disease progression in patients with colorectal cancer (CRC).

Materials and methods

The immunohistochemical expression of TGF-β1, TGFβRII, Smad4, Smad7, HLA-DR antigen, CD1a, CD83, and CD68 was evaluated in 142 patients (50 females and 92 males) with CRC, followed-up for 6–8 years period.

Results

In our study, 127 (89.4%) out of 142 colorectal cancers displayed cytoplasmic TGF-β1 immunoreactivity. Common-mediator Smad4 was detected in the tumor cytoplasm in 124 cancers (79.5%) and inhibitory Smad7 immunostaining was observed in 110 (77.4%) tumor specimens. TGFβRII was expressed on tumor cell membranes in 119 (76.3%) of the cancers. The increased TGF-β1 expression in tumor cytoplasm was related to low CD68+- and CD83+-cell infiltration in tumor tissues. Patients with TGF-β1 overexpression had worse prognosis after surgical therapy compared to those with low expression of TGF-β1. The observed association was more pronounced for the patients in T1–T2 stage (p = 0.0015).

Conclusions

The expression of TGF-β1, its receptor TGFβRII, and signaling proteins Smad4 and Smad7 was observed in the majority of colorectal cancer specimens. Our results suggest that TGF-β1 production by tumor cells may affect the tumor environment via suppression of tumor-infiltrating immune cells and probably contributes to tumor cells aggressiveness through autocrine activation of Smad signaling.
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Metadata
Title
Role of TGF-β1, its receptor TGFβRII, and Smad proteins in the progression of colorectal cancer
Authors
Maya Gulubova
Irena Manolova
Julian Ananiev
Alexander Julianov
Yovcho Yovchev
Katya Peeva
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 5/2010
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-010-0906-9

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