Chromosome 18 suppresses prostate cancer metastases.
Loss of heterozygosity and allelic imbalance data has shown that there are two distinct regions of loss on chromosome 18q associated with the progression of prostate cancer (CaP). To investigate the functional significance of chromosome 18q loci in CaP, we utilized the technique of microcell-mediated chromosome transfer to introduce an intact chromosome 18 into the human prostate cancer cell line, PC-3. Three of the resulting hybrid lines were compared to the PC-3 cells in vitro and in vivo. The hybrid cell lines, containing an intact copy of the introduced chromosome 18, exhibited a substantial reduction in anchorage-dependent and independent growth in vitro. These hybrid cell lines also made smaller tumors in nude mice following subcutaneous injection compared to PC-3 cells. Because tumor growth was not completely eliminated by introduction of chromosome 18, we assessed the ability of the hybrids to metastasize to bone after intra-cardiac inoculation in a nude mouse model. Mice inoculated with PC-3 hybrids containing intact copies of chromosome 18 had significantly fewer bone metastases and dramatically improved survival compared to PC-3 cells. In addition, the introduction of chromosome 18 significantly reduced tumor burden in extraskeletal sites. This was not because of differences in growth rates because mice bearing hybrids were monitored for metastases over twice as long as mice bearing PC-3 cells. Taken together, these data suggest that chromosome 18 has a functional role in CaP to suppress growth and metastases. Identification of the responsible gene(s) may lead to molecular targets for drug discovery.
Padalecki
S S
SS
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Weldon
K S
KS
Reveles
X T
XT
Buller
C L
CL
Grubbs
B
B
Cui
Y
Y
Yin
J J
JJ
Hall
D C
DC
Hummer
B T
BT
Weissman
B E
BE
Dallas
M
M
Guise
T A
TA
Leach
R J
RJ
Johnson-Pais
T L
TL
D000362:Agar / Q000737:chemistry; D000483:Alleles; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002871:Chromosome Banding; D002887:Chromosomes, Human, Pair 18; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics*; D013997:Time Factors; D014965:X-Rays
D000362:Agar