A three-dimensional (3D) integrated rotating-wall vessel cell-culture system was used to evaluate the interaction between a human prostate cancer cell line, LNCaP, and microcarrier beads alone, or microcarrier beads previously seeded with either prostate or bone stromal cells. Upon coculture of LNCaP cells with microcarrier beads either in the presence or in the absence of prostate or bone stromal cells, 3D prostate organoids were formed with the expected hormonal responsiveness to androgen, increased cell growth, and prostate-specific antigen production. In this communication, we define permanent 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, we observed selective genetic changes, i.e., chromosomal losses or gains, as evaluated by both conventional cytogenetic and comparative genomic hybridization, in LNCaP sublines derived from the prostate organoids. Moreover, the derivative LNCaP cells appear to have altered growth profiles, and exhibit permanent and stable changes in response to androgen, estrogen, and growth factors. The derivative LNCaP sublines showed increased anchorage-independent growth rate, and enhanced tumorigenicity and metastatic potential when inoculated orthotopically in castrated athymic mice. Our results support the hypothesis that further nonrandom genetic and phenotypic changes in prostate cancer epithelial cells can occur through an event that resembles “adaptive mutation” such as has been described in bacteria subjected to nutritional starvation. The occurrence of such permanent changes may be highly contact dependent, and appears to be driven by specific microenvironmental factors surrounding the tumor cell epithelium grown as 3D prostate organoids.
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1 March 2001
PERMANENT PHENOTYPIC AND GENOTYPIC CHANGES OF PROSTATE CANCER CELLS CULTURED IN A THREE-DIMENSIONAL ROTATING-WALL VESSEL
HONG W. RHEE,
HAIYEN E. ZHAU,
SEN PATHAK,
ASHA S. MULTANI,
SARI PENNANEN,
TAPIO VISAKORPI,
LELAND W. K. CHUNG
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In Vitro Cellular & Developmental Biology - Animal
Vol. 37 • No. 3
March 2001
Vol. 37 • No. 3
March 2001
anchorage-dependent and -independent growth
chromosomal losses and gains
EGF, bFGF, KGF, HGF/SF, IGF-1 growth factors
microgravity-simulated cell culture
prostate cancer cells in 3D culture
prostate cancer metastasis
prostate cancer models