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Int J Colorectal Dis. 2010 May;25(5):591-9. doi: 10.1007/s00384-010-0906-9. Epub 2010 Feb 18.

Role of TGF-beta1, its receptor TGFbetaRII, and Smad proteins in the progression of colorectal cancer.

Author information

1
Department of General and Clinical Pathology, Medical Faculty, Trakia University, Stara Zagora, 11 Armeiska Str, 6000, Stara Zagora, Bulgaria. decan@mf.uni-sz.bg

Abstract

AIM:

In the current study, we investigated the expression of TGF-beta1, its receptor TGFbetaRII, 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-beta1, TGFbetaRII, 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-beta1 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. TGFbetaRII was expressed on tumor cell membranes in 119 (76.3%) of the cancers. The increased TGF-beta1 expression in tumor cytoplasm was related to low CD68(+)- and CD83(+)-cell infiltration in tumor tissues. Patients with TGF-beta1 overexpression had worse prognosis after surgical therapy compared to those with low expression of TGF-beta1. The observed association was more pronounced for the patients in T1-T2 stage (p = 0.0015).

CONCLUSIONS:

The expression of TGF-beta1, its receptor TGFbetaRII, and signaling proteins Smad4 and Smad7 was observed in the majority of colorectal cancer specimens. Our results suggest that TGF-beta1 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.

PMID:
20165854
DOI:
10.1007/s00384-010-0906-9
[Indexed for MEDLINE]

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