Primary cell cultures as models of prostate cancer development

Abstract

This review focuses on primary cultures of human prostatic epithelial cells and their applications as models of normal and malignant biological behavior. Current abilities to culture cells from normal tissues, from premalignant dysplastic lesions (prostatic intraepithelial neoplasia), from primary adenocarcinomas, and from metastases are described. Evidence for representation of the interrelated cells of the normal prostatic epithelium -stem cells, basal epithelial cells, secretory epithelial cells, transit amplifying cells and neuroendocrine cells -in primary cultures is presented. Comparisons between normal and cancer-derived primary cultures are made regarding biological activities relevant to carcinogenesis, such as proliferation, apoptosis, differentiation, senescence, adhesion, migration, invasion, steroid hormone metabolism, other metabolic pathways and angiogenesis. Analyses of tumor suppressor activity, differential gene expression and cytogenetics in primary cultures have revealed changes relevant to prostate cancer progression. Preclinical studies with primary cultures have provided information useful for designing new strategies for chemoprevention, chemotherapy, cytotoxin therapy, radiation therapy, gene therapy and imaging. While the behavior of normal primary cultures is often used as a basis for comparison with established, immortal prostate cancer cell lines, the most informative studies are performed with donor-matched pairs of normal and malignant primary cultures, grown under identical conditions. Challenges that remain to be addressed if the full potential of primary cultures as a model system is to be realized include isolation, culture and characterization of stem cells, improved methodology to induce or maintain a fully differentiated, androgen-responsive phenotype, and identification of cell surface antigens or other markers with which to purify pure populations of live cancer or premalignant cells apart from non-malignant epithelial cells prior to culture.

Epithelial-Restricted Gene Profile of Primary Cultures from Human Prostate Tumors: A Molecular Approach to Predict Clinical Behavior of Prostate Cancer

“…Cultures from normal/hyperplastic tissue (N1, C10, C17, and C16sx) and cancer had similar growth rate (10,11). Importantly, all cultures had limited life span (20-25 population doublings) and similar cell morphology, as described (12). Cells were elongated and formed tight, cohesive islands (data not shown).…”

In vitro model systems to study androgen receptor signaling in prostate cancer

“…The underlying reason for these apparent conflicting findings remains unclear, although it may be noted that the transcriptome of stromal AR remains poorly studied, at least in part because only a subpopulation of stromal cells expresses AR, which additionally appear to require paracrine-acting epithelial signals (Lang et al 2001, Cano et al 2007, Berry et al 2011. In general, most immortalized stromal cell lines express only low or undetectable levels of AR (Peehl 2005, Kogan et al 2006. Consequently, most studies analyzing the role of stromal AR in prostate development and carcinogenesis have utilized mouse urogenital sinus mesenchyme (Shaw et al 2006, Cunha 2008.…”

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

“…Stromal cells were separated from epithelial cells by discontinuous gradient centrifugation. 23 The stromal cells derived from the PZ (PZsc) and stromal cells derived from the TZ (TZsc) were identified by immunocytochemistry (IHC) 8 and cultured with RPMI 1640 supplemented with 10% foetal bovine serum (Gibco, Melbourne, Australia) and antibiotics (100 mg ml 21 streptomycin and 100 IU ml 21 penicillin) (Gibco BRL, Grand Island, NY, USA) at 37 uC under 5% CO 2 and a humidified atmosphere. The stromal cells were used at passages 3-5.…”