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

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.

• Authors: Maya Gulubova, Irena Manolova, Julian Ananiev, Alexander Julianov, Yovcho Yovchev, Katya Peeva
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 25 Issue 5 Pg. 591-9 (May 2010) ISSN: 1432-1262 [Electronic] Germany
• PMID: 20165854 (Publication Type: Journal Article)

Chemical References

• Neoplasm Proteins
• Receptors, Transforming Growth Factor beta
• SMAD4 protein, human
• SMAD7 protein, human
• Smad4 Protein
• Smad7 Protein
• Transforming Growth Factor beta1
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigen-Presenting Cells (metabolism, pathology)
• Cell Count
• Cell Membrane (metabolism)
• Colorectal Neoplasms (metabolism, pathology)
• Disease Progression
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Protein Transport
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (metabolism)
• Smad4 Protein (metabolism)
• Smad7 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)