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. 1999 Apr;79(11-12):1651–1656. doi: 10.1038/sj.bjc.6690264

Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells

H Miyake 1, I Hara 1, K Yamanaka 1, K Gohji 1, S Arakawa 1, S Kamidono 1
PMCID: PMC2362776  PMID: 10206273

Abstract

We investigated the effect of Bcl-2 expression on the metastatic process of bladder cancer cells by using the Bcl-2-transfected human bladder cancer cell lines (KoTCC-1/BH) and the control vector only-transfected cell line (KoTCC-1/C), which were generated in our previous study (Miyake et al (1998) Oncogene 16: 933–934). When they were injected intravenously into athymic nude mice, KoTCC-1/BH formed more than three times as many tumour nodules in the lungs as did KoTCC-1/C. In addition, tumour progression, including lymph node metastasis and haemorrhagic ascites, was observed to be more advanced after the implantation of KoTCC-1/BH cells into the bladder wall of nude mice than after implantation of KoTCC-1/C cells. These enhanced malignant progression of KoTCC-1/BH cells were well correlated with anti-apoptotic activity under anchorage-independent conditions in in vitro experimental models. In contrast, there were no significant differences among these cell lines in their growth rates both in vitro and in vivo, invasive ability and cell motility. These findings suggest that, if it is overexpressed, Bcl-2 prolongs cell survival under unfavourable conditions encountered in the metastatic process, resulting in the enhanced metastatic potential of bladder cancer. © 1999 Cancer Research Campaign

Keywords: Bcl-2, metastasis, apoptosis, bladder cancer

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Selected References

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  1. Albini A., Iwamoto Y., Kleinman H. K., Martin G. R., Aaronson S. A., Kozlowski J. M., McEwan R. N. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987 Jun 15;47(12):3239–3245. [PubMed] [Google Scholar]
  2. Crowley C. W., Cohen R. L., Lucas B. K., Liu G., Shuman M. A., Levinson A. D. Prevention of metastasis by inhibition of the urokinase receptor. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5021–5025. doi: 10.1073/pnas.90.11.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dinney C. P., Fishbeck R., Singh R. K., Eve B., Pathak S., Brown N., Xie B., Fan D., Bucana C. D., Fidler I. J. Isolation and characterization of metastatic variants from human transitional cell carcinoma passaged by orthotopic implantation in athymic nude mice. J Urol. 1995 Oct;154(4):1532–1538. [PubMed] [Google Scholar]
  4. Ellis R. E., Yuan J. Y., Horvitz H. R. Mechanisms and functions of cell death. Annu Rev Cell Biol. 1991;7:663–698. doi: 10.1146/annurev.cb.07.110191.003311. [DOI] [PubMed] [Google Scholar]
  5. Fidler I. J., Balch C. M. The biology of cancer metastasis and implications for therapy. Curr Probl Surg. 1987 Mar;24(3):129–209. doi: 10.1016/0011-3840(87)90002-5. [DOI] [PubMed] [Google Scholar]
  6. Gallo O., Boddi V., Calzolari A., Simonetti L., Trovati M., Bianchi S. bcl-2 protein expression correlates with recurrence and survival in early stage head and neck cancer treated by radiotherapy. Clin Cancer Res. 1996 Feb;2(2):261–267. [PubMed] [Google Scholar]
  7. Inbal B., Cohen O., Polak-Charcon S., Kopolovic J., Vadai E., Eisenbach L., Kimchi A. DAP kinase links the control of apoptosis to metastasis. Nature. 1997 Nov 13;390(6656):180–184. doi: 10.1038/36599. [DOI] [PubMed] [Google Scholar]
  8. King E. D., Matteson J., Jacobs S. C., Kyprianou N. Incidence of apoptosis, cell proliferation and bcl-2 expression in transitional cell carcinoma of the bladder: association with tumor progression. J Urol. 1996 Jan;155(1):316–320. [PubMed] [Google Scholar]
  9. Miyake H., Hanada N., Nakamura H., Kagawa S., Fujiwara T., Hara I., Eto H., Gohji K., Arakawa S., Kamidono S. Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer. Oncogene. 1998 Feb 19;16(7):933–943. doi: 10.1038/sj.onc.1201602. [DOI] [PubMed] [Google Scholar]
  10. Miyake H., Hara I., Gohji K., Yoshimura K., Arakawa S., Kamidono S. Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer cell line. Cancer Lett. 1998 Jan 30;123(2):121–126. doi: 10.1016/s0304-3835(97)00365-0. [DOI] [PubMed] [Google Scholar]
  11. Miyake H., Hara I., Yoshimura K., Eto H., Arakawa S., Wada S., Chihara K., Kamidono S. Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential. Cancer Res. 1996 May 15;56(10):2440–2445. [PubMed] [Google Scholar]
  12. Miyake H., Yoshimura K., Hara I., Eto H., Arakawa S., Kamidono S. Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines. J Urol. 1997 Jun;157(6):2351–2355. [PubMed] [Google Scholar]
  13. Nikiforov M. A., Hagen K., Ossovskaya V. S., Connor T. M., Lowe S. W., Deichman G. I., Gudkov A. V. p53 modulation of anchorage independent growth and experimental metastasis. Oncogene. 1996 Oct 17;13(8):1709–1719. [PubMed] [Google Scholar]
  14. Shtivelman E. A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma. Oncogene. 1997 May 8;14(18):2167–2173. doi: 10.1038/sj.onc.1201059. [DOI] [PubMed] [Google Scholar]
  15. Takaoka A., Adachi M., Okuda H., Sato S., Yawata A., Hinoda Y., Takayama S., Reed J. C., Imai K. Anti-cell death activity promotes pulmonary metastasis of melanoma cells. Oncogene. 1997 Jun 19;14(24):2971–2977. doi: 10.1038/sj.onc.1201147. [DOI] [PubMed] [Google Scholar]
  16. Thrasher J. B., Crawford E. D. Current management of invasive and metastatic transitional cell carcinoma of the bladder. J Urol. 1993 May;149(5):957–972. doi: 10.1016/s0022-5347(17)36270-5. [DOI] [PubMed] [Google Scholar]
  17. Tsuchiya Y., Sato H., Endo Y., Okada Y., Mai M., Sasaki T., Seiki M. Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo. Cancer Res. 1993 Mar 15;53(6):1397–1402. [PubMed] [Google Scholar]
  18. Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]

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