Permanent phenotypic and genotypic changes of prostate cancer cells cultured in a three-dimensional rotating-wall vessel

Rhee, HW Zhau, HE Pathak, S Multani, AS Pennanen, S Visakorpi, T Chung, LWK

Hw. Rhee et al., Permanent phenotypic and genotypic changes of prostate cancer cells cultured in a three-dimensional rotating-wall vessel, IN VITRO-AN, 37(3), 2001, pp. 127-140

40

INGLESE

Article

Cell & Developmental Biology

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL

1071-2690 → ACNP

37

3

2001

127 - 140

ISI

1071-2690(200103)37:3<127:PPAGCO>2.0.ZU;2-M

A three-dimensional (3D) integrated rotating-wall vessel cell-culture sr;st em was used to evaluate the interaction between a human prostate cancer cel l line, LNCaP, and microcarrier heads alone, or microcarrier beads previous ly seeded with either prostate or bone stromal cells. Upon coculture of LNC aP cells with microcarrier beads either in the presence or in the absence o f prostate or bone stromal cells, 3D prostate organoids were formed with th e expected hormonal responsiveness to androgen, increased cell growth, anti prostate-specific antigen production. in this communication, we define per manent phenotypic and genotypic changes of LNCaP cells upon coculture with microcarrier beads alone, or with microcarrier beads previously seeded with either prostate or bone stromal cells, Most notably, rye observed selectiv e genetic changes, i.e., chromosomal losses or gains, as evaluated by both conventional cytogenetic and comparative genomic hybridization, in LNCaP su blines derived from the prostate organoids. Moreover, the derivative LNCaP cells appear to hare altered growth profiles, and exhibit permanent and sta ble changes in response to androgen, estrogen, and growth factors. The deri vative LNCaP sublines showed increased anchorage-independent growth rate, a nd enhanced tumorigenicity and metastatic potential when inoculated orthoto pically in castrated athymic mice. Our results support the hypothesis that further nonrandom genetic and phenotypic changes in prostate cancer epithel ial cells can occur through an event that resembles "adaptive mutation" suc h as has been described in bacteria subjected to nutritional starvation. Th e occurrence of such permanent changes may be highly contact dependent, and appears to be driven by specific micro environmental factors surrounding t he tumor cell epithelium grown as 3D prostate organoids.