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Expression of transforming growth factor beta type II receptors in head and neck squamous cell carcinoma
C A Muro-Cacho1, M Anderson, J Cordero
1Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Biochemistry and Molecular Biology, University of South Florida, Tampa 33612, USA.
Abstract:
Transforming growth factor (TGF)-beta is a potent regulator of growth and differentiation in normal squamous epithelium. TGF-beta exerts its antiproliferative effect via the TGF-beta type II receptor (TbetaR-II). A decrease in TbetaR-II expression is believed to be responsible, in part, for the resistance of squamous cell carcinoma (SqCC) to the anti-proliferative effects of TGF-beta. In the present study, we used immunohistochemistry and in situ hybridization to analyze the expression of TbetaR-II along the successive oncogenic stages of head and neck squamous neoplasia, from normal epithelium to dysplasia to carcinoma. Quantitation of TbetaR-II expression in 38 SqCCs was assessed on a visual scale ranging from negative (absence of staining) to 3+ (strong staining). Normal squamous epithelium and squamous epithelium in the vicinity of the tumors showed homogenous receptor expression with moderate intensity. Dysplastic epithelium and carcinoma in situ showed a mild decrease in receptor expression intensity. Well-differentiated to moderately differentiated carcinomas showed heterogeneous expression of variable intensity, and poorly differentiated carcinomas were completely devoid of TbetaR-II. In every tumor, the superficial component showed more intense receptor expression than the invasive component. These results indicate that TbetaR-II expression inversely correlates with disease aggressiveness and suggest that aberrant TbetaR-II expression is a contributing factor to the pathogenesis of SqCC.
Insights
Transforming growth factor-beta type II receptor (TbetaR-II) expression decreases with increasing head and neck squamous cell carcinoma aggressiveness. Reduced TbetaR-II is linked to cancer progression and resistance to TGF-beta
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor-beta (TGF-beta) regulates squamous epithelium growth and differentiation.
- TGF-beta signals through the TGF-beta type II receptor (TbetaR-II).
- Decreased TbetaR-II expression is implicated in squamous cell carcinoma (SqCC) resistance to TGF-beta's antiproliferative effects.
Purpose of the Study:
- To analyze TbetaR-II expression across oncogenic stages of head and neck squamous neoplasia.
- To correlate TbetaR-II expression levels with SqCC aggressiveness and differentiation.
Main Methods:
- Immunohistochemistry and in situ hybridization were used to assess TbetaR-II expression.
- TbetaR-II expression was quantified on a scale from negative to 3+ in 38 SqCCs.
- Expression patterns were analyzed from normal epithelium to dysplasia, carcinoma in situ, and invasive SqCC.
Main Results:
- Normal and adjacent squamous epithelium showed homogenous, moderate TbetaR-II expression.
- Dysplastic epithelium and carcinoma in situ exhibited a mild decrease in TbetaR-II intensity.
- Poorly differentiated SqCCs were devoid of TbetaR-II, while well-differentiated tumors showed heterogeneous expression; superficial components had higher expression than invasive ones.
Conclusions:
- TbetaR-II expression inversely correlates with the aggressiveness of head and neck SqCC.
- Aberrant TbetaR-II expression is a significant factor in the pathogenesis of SqCC.
- Loss of TbetaR-II may contribute to tumor progression and therapeutic resistance.