Characterization of Reactive Stroma in Human Prostate Cancer and Role of Prostate Cancer Stem Cells (PCSCs), Growth Factors, Matrix Metalloproteinases (MMPs) and Steroid Hormone Receptors (SHRs) in Its Pathogenesis
Wagner J Favaro, Athanase Billis, Luciana Meirelles, Leandro LLL Freitas, Leonardo O Reis, Ubirajara Ferreira. School of Medicine, University of Campinas (Unicamp), Campinas, SP, Brazil; School of Medicine (UNESP), Botucatu, SP, Brazil
Background: Reactive stroma occurs in many human cancers and it is likely to promote tumorigenesis. The aim of this study was to characterize the reactive stroma environment and to find any association of PCSCs, MMPs, SHRs and growth factors in its pathogenesis.
Design: Reactive stroma was evaluated in 20 needle prostatic biopsies, and divided into 2 groups: cancer without reactive stroma (Group 1); and cancer with intense reactive stroma (Group 2). The samples were submitted to morphological and immunohistochemical analyses for smooth muscle (SM) α-actin, vimentin, androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), fibroblast growth factor 2 (FGF-2), insulin like growth factor 1 (IGF-1), MMP-2, CD44, CD133, p63, Prostate Stem Cell Antigen (PSCA), ATP-binding cassette membrane transporter (ABCG2) and C-Myc.
Results: There was increased collagen fibers and decreased smooth muscle cells in Group 2. In Group 2 vimentin and SM α-actin were positive, indicating a myofibroblast phenotype. PCSCs of the epithelial compartment were ABCG2/PSCA/C-Myc/CD44/CD133/p63/ERα+ and in the stroma were ABCG2/C-Myc/CD133/Vimentin/ERα+. These cells had intense immunoreactivity in Group 2 comparing to Group 1. IGF-1, FGF-2 and MMP-2 were significantly higher in Group 2. Intensified AR was verified in the epithelial compartment from all groups. However, this receptor was only intense in the stromal compartment in Group 2. ERα immunoreactivity was more intense in the stromal compartment from Group 2 in relation to Group 1. ERβ was present mainly in the epithelial compartment and only in the stromal compartment of Group 2.
Conclusions: Reactive stroma was composed of myofibroblasts and fibroblasts stimulated to express extracellular matrix components. Intensified FGF, IGF and MMP immunoreactivities certainly compromised the glandular epithelial-stromal interaction and could be considered as regulators of reactive stroma. PCSCs were intensely associated with reactive stroma. The dynamic paracrine signaling of the SHRs discloses the role of these hormones in the activation mechanisms of reactive stroma and occurrence of PCSCs. Thus, it can be concluded that reactive stroma may be considered an important biological component of prostatic cancer.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 123, Wednesday Morning