Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa

  • Authors:
    • Graziella Bellone
    • Claudia Gramigni
    • Barbara Vizio
    • Francesco A. Mauri
    • Adriana Prati
    • Dino Solerio
    • Luca Dughera
    • Enrico Ruffini
    • Guido Gasparri
    • Michele Camandona
  • View Affiliations

  • Published online on: November 1, 2010     https://doi.org/10.3892/ijo_00000767
  • Pages: 1153-1165
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Abstract

The precise timing of the angiogenic switch in colorectal cancer development is still unclear. The simultaneous expression of Endoglin (CD105), transforming growth factor (TGF)-β1 and TGF-β receptor (R) II were quantified in surgical specimens comprising normal human colon, pre-malignant dysplastic tissue, in situ, and invasive colon cancer specimens, at mRNA and protein levels, respectively by real-time PCR and immunohistochemistry. Serum concentrations of soluble Endoglin and TGF-β1 were evaluated. mRNA and CD105+-microvessel density (MVD) increased significantly in dysplastic colon and carcinoma versus normal tissues; values correlated respectively with dysplasia degree and Dukes' stages. TGF-β1 expression was significantly upregulated in most severe dysplastic adenoma specimens, while TGF-β1 transcript and protein signals were intense in carcinoma, positively-correlated with tumor progression. TGF-β1 RII was overexpressed in adenoma and carcinoma versus normal samples, but unrelated with dysplasia or Dukes' stage. Soluble Endoglin serum levels were equivalent in adenoma and normal tissues; in carcinoma the highest levels were in invasive tumor. Circulating TGF-β1 levels were increased in severe dysplasia and progressed with tumor progression. Correlations between adenoma dysplasia degree and TGF-β RII and CD105+-MVD, and between tumor Dukes' staging and TGF-β1 and CD105+-MVD, were significant. TGF-β1 and Endoglin and TGF-β1 serum levels, TGF-β1 staining and CD105+-MVD were significantly and inversely associated with disease-free survival. TGF-β1 levels were an independent and significant prognostic factor of disease-free survival. These findings suggest active angiogenesis occurs in many pre-malignant colon cases and supports more careful evaluation of different chemopreventive agents.

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November 2010
Volume 37 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Bellone G, Gramigni C, Vizio B, Mauri FA, Prati A, Solerio D, Dughera L, Ruffini E, Gasparri G, Camandona M, Camandona M, et al: Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa. Int J Oncol 37: 1153-1165, 2010
APA
Bellone, G., Gramigni, C., Vizio, B., Mauri, F.A., Prati, A., Solerio, D. ... Camandona, M. (2010). Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa. International Journal of Oncology, 37, 1153-1165. https://doi.org/10.3892/ijo_00000767
MLA
Bellone, G., Gramigni, C., Vizio, B., Mauri, F. A., Prati, A., Solerio, D., Dughera, L., Ruffini, E., Gasparri, G., Camandona, M."Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa". International Journal of Oncology 37.5 (2010): 1153-1165.
Chicago
Bellone, G., Gramigni, C., Vizio, B., Mauri, F. A., Prati, A., Solerio, D., Dughera, L., Ruffini, E., Gasparri, G., Camandona, M."Abnormal expression of Endoglin and its receptor complex (TGF-β1 and TGF-β receptor II) as early angiogenic switch indicator in premalignant lesions of the colon mucosa". International Journal of Oncology 37, no. 5 (2010): 1153-1165. https://doi.org/10.3892/ijo_00000767