Novel Prostate Cancer Stem Cells (PCSC) Signaling Pathways: Implications of Toll-Like Receptors (TLRs) and Steroid Hormone Receptors (SHRs)
Wagner J Favaro, Athanase Billis, Ubirajara Ferreira. School of Medicine, University of Campinas (Unicamp), Campinas, SP, Brazil
Background: TLR signaling can promote opposite outcomes: tumor growth and immune evasion or apoptosis and cell cycle arrest. Steroid hormones are responsible for morphological and physiological prostatic maintenance. Also, PCSC is an important step for cancer pathogenesis.
Design: Sixty prostate sections from men 60 to 90-year-old were divided into 4 groups: no lesions (Group 1); with NH (Group 2); with HGPIN (Group 3); and, with CA (Group 4). The sections were submitted to immunohistochemistry and Western Blotting analysis for androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), TLR2, TLR4, NF-kB, MyD88, CD44, CD133, p63, ATP-binding cassette membrane transporter (ABCG2), C-Myc, Antigen Stem Cell Prostate (PSCA) and Vimentin.
Results: Intensified AR immunoreactivity was verified in the epithelial compartment from all groups. However, this receptor was only intense in the stromal compartment in Groups 2, 3 and 4. ERα immunoreactivity was intense in the epithelial and stromal compartments from Groups 2, 3, and 4. ERβ was present mainly in the epithelial compartment and only in the stromal compartment of Group 4. TLR 2, 4 and MyD88 protein levels were significantly lower in the Groups 3 and 4 when related to Groups 1 and 2. NF-kB protein level was significantly higher in the Groups 3 and 4. PCSC were more frequently seen in the epithelial compartment of Groups 4 and 3 comparing to Group 2. PCSC of the epithelial compartment were ABCG2/PSCA/C-Myc/CD44/CD133/p63/ERα+ and PCSC of the stroma were and ABCG2/C-Myc/CD133/Vimentin/ERα+. PCSC were absent in the Group 1.
Conclusions: Expression of TLR 2, 4 and MyD88 were decreased in prostatic lesions, especially in prostate cancer, indicating an important role in the regulation of prostatic carcinogenesis. ERβ showed stimulatory effect on TLR-MyD88 signals that correlated with the decreased of histopathological grade. NH, HGPIN, and CA were characterized by distinct ERα and ERβ reactivities in both epithelial and stromal compartment, as well as higher NF-kB protein level, indicating an important signaling for PCSC. The dynamic signaling of the SHRs and TLR-MyD88 signals discloses the role of these molecular features in the activation mechanisms of PCSC in prostatic lesions and may be crucial for the development of therapy in malignant prostatic diseases.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 74, Tuesday Morning