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

  • Maya GulubovaEmail author
  • Irena Manolova
  • Julian Ananiev
  • Alexander Julianov
  • Yovcho Yovchev
  • Katya Peeva
Original Article



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.


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).


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.


Colorectal cancer TGF-β TGFβRII Smad proteins Dendritic cells Macrophages 


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Maya Gulubova
    • 1
    Email author
  • Irena Manolova
    • 2
  • Julian Ananiev
    • 1
  • Alexander Julianov
    • 3
  • Yovcho Yovchev
    • 3
  • Katya Peeva
    • 4
  1. 1.Department of General and Clinical Pathology, Medical FacultyTrakia UniversityStara ZagoraBulgaria
  2. 2.Laboratory of Clinical Immunology, Medical FacultyTrakia UniversityStara ZagoraBulgaria
  3. 3.Department of Surgery, University Hospital, Medical FacultyTrakia UniversityStara ZagoraBulgaria
  4. 4.Department of Informatics and Biostatistics, Medical FacultyTrakia UniversityStara ZagoraBulgaria

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