Chromosome 18 suppresses prostate cancer metastases

S. S. Padalecki, K. S. Weldon, X. T. Reveles, C. L. Buller, B. Grubbs, Y. Cui, J. J. Yin, D. C. Hall, B. T. Hummer, B. E. Weissman, M. Dallas, Theresa Guise, R. J. Leach, T. L. Johnson-Pais

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)366-373
Number of pages8
JournalUrologic Oncology: Seminars and Original Investigations
Volume21
Issue number5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 18
Prostatic Neoplasms
Neoplasm Metastasis
Hybrid Cells
Chromosomes
Growth
Nude Mice
Cell Line
Allelic Imbalance
Bone and Bones
Loss of Heterozygosity
Drug Discovery
Subcutaneous Injections
Tumor Burden
Neoplasms
Survival
Genes

Keywords

  • Chromosome 18
  • Metastasis
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Padalecki, S. S., Weldon, K. S., Reveles, X. T., Buller, C. L., Grubbs, B., Cui, Y., ... Johnson-Pais, T. L. (2003). Chromosome 18 suppresses prostate cancer metastases. Urologic Oncology: Seminars and Original Investigations, 21(5), 366-373. https://doi.org/10.1016/S1078-1439(03)00013-9

Chromosome 18 suppresses prostate cancer metastases. / Padalecki, S. S.; Weldon, K. S.; Reveles, X. T.; Buller, C. L.; Grubbs, B.; Cui, Y.; Yin, J. J.; Hall, D. C.; Hummer, B. T.; Weissman, B. E.; Dallas, M.; Guise, Theresa; Leach, R. J.; Johnson-Pais, T. L.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 21, No. 5, 09.2003, p. 366-373.

Research output: Contribution to journalArticle

Padalecki, SS, Weldon, KS, Reveles, XT, Buller, CL, Grubbs, B, Cui, Y, Yin, JJ, Hall, DC, Hummer, BT, Weissman, BE, Dallas, M, Guise, T, Leach, RJ & Johnson-Pais, TL 2003, 'Chromosome 18 suppresses prostate cancer metastases', Urologic Oncology: Seminars and Original Investigations, vol. 21, no. 5, pp. 366-373. https://doi.org/10.1016/S1078-1439(03)00013-9
Padalecki, S. S. ; Weldon, K. S. ; Reveles, X. T. ; Buller, C. L. ; Grubbs, B. ; Cui, Y. ; Yin, J. J. ; Hall, D. C. ; Hummer, B. T. ; Weissman, B. E. ; Dallas, M. ; Guise, Theresa ; Leach, R. J. ; Johnson-Pais, T. L. / Chromosome 18 suppresses prostate cancer metastases. In: Urologic Oncology: Seminars and Original Investigations. 2003 ; Vol. 21, No. 5. pp. 366-373.
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