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Published on: October 27, 2020
Modulation of phenotype of human prostatic stromal cells by transforming growth factor-betas
Toshihiro Hisataki1, Naoki Itoh, Kazuhiro Suzuki
1Department of Urology, Sapporo Medical University, Sapporo, Japan.
Background:
We investigated the effects of transforming growth factor (TGF)-betas on morphological and receptor phenotypes, as well as proliferation of four currently established human prostatic myofibroblast cell lines and one commercially available prostatic stromal cell line.
Methods:
The effects of TGF-betas on morphological changes and proliferation of the cells were studied by immunohistochemistry and bromodeoxyuridine assay, respectively. The expression of alpha 1-receptor subtypes was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the radioligand binding assay for the receptors was also performed.
Results:
TGF-betas 1, 2, and 3 induced expression of desmin and myosin of cells of the established cell lines, and significantly inhibited their growth. The alpha 1a-receptor was expressed only in the commercially available cell line and alpha 1b and 1d, in all cell lines. TGF-beta 1 suppressed the expression of all three subtypes of the alpha 1-receptor. The binding sites of cells of all the cell lines were reduced by treatment with this growth factor.
Conclusions:
TGF-betas may induce human prostatic stromal cells to express the smooth muscle phenotype and inhibited their growth. However, the growth factor reduced the binding sites of the receptor and suppressed mRNA expression of its subtypes, suggesting that morphological and receptor phenotypes may be regulated via more than one pathway by TGF-beta(s).
Insights
Transforming growth factor-betas (TGF-betas) can induce smooth muscle phenotypes in human prostatic stromal cells and inhibit their growth. However, TGF-betas also reduce receptor binding sites and suppress mRNA expression, indicating complex regulatory pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Prostate Cancer Research
Background:
- Investigated the impact of transforming growth factor-betas (TGF-betas) on human prostatic myofibroblast and stromal cell lines.
- Focused on morphological and receptor phenotypes, alongside cellular proliferation.
Purpose of the Study:
- To determine how TGF-betas influence the differentiation and growth of prostatic stromal cells.
- To analyze the expression and regulation of alpha 1-receptor subtypes in response to TGF-betas.
Main Methods:
- Utilized immunohistochemistry and bromodeoxyuridine assays for morphological and proliferation analysis.
- Employed real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assays to assess alpha 1-receptor subtype expression.
Main Results:
- TGF-betas 1, 2, and 3 induced desmin and myosin expression, inhibiting cell growth.
- Alpha 1a-receptors were specific to the commercial cell line, while alpha 1b and 1d were ubiquitous.
- TGF-beta 1 decreased alpha 1-receptor subtype expression and reduced binding sites across all cell lines.
Conclusions:
- TGF-betas promote a smooth muscle phenotype and inhibit growth in prostatic stromal cells.
- The observed reduction in receptor binding and mRNA expression suggests multifaceted TGF-beta signaling pathways.
- Prostatic stromal cell phenotype and receptor expression are likely regulated by multiple mechanisms involving TGF-betas.

