Genetic abnormalities specifically associated with varying metastatic potential of prostate cancer cell lines as detected by comparative genomic hybridization

Established recently are two in vivo prostate tumor progression models in w hich subclones of the PC3M and LNCaP cell lines were selected for varying g rowth characteristics and metastatic potential after successive orthotopic implantation in the prostate of nude mice. In this study, we used comparati ve genomic hybridization (CGH) to compare the chromosomal abnormalities bet ween the parental cell lines and their respective variants and to determine if specific chromosomal abnormalities can be identified that are associate d with different growth properties. PC3M and its derivative cell lines PC3M -Pro4 and PC3M-LN4 shared gains of 8q22-qter, 10q21-q22. and Xq27-qter and loss of 13q33-qter. PC3M-Pro4, a derivative line that produced significantl y larger tumors in the prostate, had a unique gain of 3q13. In contrast, PC 3M-LN4. the derivative line that produced significantly larger metastatic t umors in the lymph nodes and had higher incidences of distant metastases, h ad a specific gain of 1q21-q22 and losses of 10q23-qter and 18q12-q21. In t he second in vivo model. LNCaP and its derivative cell lines shared gain of 3q27-qter and loss on 13q21-qter. The derivative line that produced signif icantly larger tumors in the prostate. LNCaP-Pro5, had a unique gain on 13q 12-q13. In comparison, LNCaP-LN3. a derivative line that had a significantl y higher incidence of lymph node metastases and produced significantly larg er metastatic tumors in the lymph nodes. had specific losses of 16q23-qter and 21q. Interestingly, some regions of loss (e.g., 10q23 --> qter. 16q23 - -> qter. and 18q12 --> q21) detected in the variant cell lines correlated w ell with abnormalities seen in clinical prostate cancer cases. Thus, our da ta suggest not only that these cell lines are relevant in vivo models for p rostate cancer progression, but also that CGH is a valuable tool for uncove ring chromosomal regions that are important for aggressive growth and metas tsis of prostate cancer cells. (C) 2001 Elsevier Science Inc. All rights re served.