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Dysregulated expression of transforming growth factor beta and its type-I and type-II receptors in basal-cell
1Department of Dermatology, University of Tokyo, Branch Hospital, Bunkyo-ku, Japan. FURUEM-DIS@h.u-tokyo.ac.jp
Abstract:
In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated the immunohistological localization of TGF-beta1, TGF-beta2, TbetaR-I and TbetaR-II in normal human skin, basal-cell carcinoma (BCC), Bowen's disease, seborrheic keratosis, eccrine poroma and eccrine spiradenoma using frozen tissue specimens. In normal human skin, the immunoreactive TGF-beta2, but not TGF-beta1, was detected predominantly in the epidermis, follicles and sebaceous glands. The epidermal expression of TbetaR-I and TbetaR-II was very weak in the majority of normal skins. In BCC, TGF-beta2 expression was markedly reduced or completely negative. In addition, TbetaR-I- and TbetaR-II-positive stromal cells were accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly but moderately positive for TGF-beta1. Decreased expression of TGF-beta2 was likely to be associated with the differentiation state of BCC cells, since TGF-beta2 expression was clearly observed in the squamoid foci of BCC. In addition, no expression of TGF-beta2 was detected in the eccrine secretory portion or in eccrine spiradenoma, but it was detected in the upper eccrine ducts and in eccrine poroma.
Insights
Transforming growth factor-beta 2 (TGF-beta2) is reduced in basal-cell carcinoma (BCC) and eccrine tumors. TGF-beta2 expression in normal skin is mainly in the epidermis, while receptors are weakly expressed.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-beta) signaling, involving TGF-beta isoforms and type I/II receptors (TbetaR-I/TbetaR-II), regulates keratinocyte growth and metabolism.
- TGF-beta isoforms and their receptors play crucial roles in skin biology and disease pathogenesis.
Purpose of the Study:
- To investigate the immunohistological localization of TGF-beta1, TGF-beta2, TbetaR-I, and TbetaR-II in normal human skin and various skin tumors.
- To understand the role of TGF-beta signaling in the development and progression of skin cancers like basal-cell carcinoma (BCC).
Main Methods:
- Immunohistochemical analysis of frozen tissue specimens from normal skin, BCC, Bowen's disease, seborrheic keratosis, eccrine poroma, and eccrine spiradenoma.
- Detection and localization of TGF-beta1, TGF-beta2, TbetaR-I, and TbetaR-II expression within different skin layers and tumor cells.
Main Results:
- In normal skin, TGF-beta2 was predominantly found in the epidermis, follicles, and sebaceous glands, while TbetaR-I and TbetaR-II showed weak epidermal expression.
- BCC exhibited markedly reduced or absent TGF-beta2 expression, particularly in non-squamoid areas, suggesting a link to differentiation.
- TGF-beta2 was absent in eccrine secretory portions and eccrine spiradenoma but present in upper eccrine ducts and eccrine poroma.
Conclusions:
- The altered expression of TGF-beta2 in BCC may correlate with tumor differentiation and progression.
- TGF-beta signaling components show differential localization in normal skin appendages and specific skin tumors.
- Further research into TGF-beta's role could offer insights into therapeutic strategies for skin cancers.