Advertisement

Novel Human Prostate Epithelial Cell Cultures

  • Johng S. Rhim
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1164)

Abstract

Prostate cancer is the most common male cancer in the USA and the second leading cause of male cancer death in the USA. African American men have higher incidence and mortality rate from prostate cancer compared to Caucasian men in North America, indicating the prostate cancer is a major public health problem in this population. Studies of prostate cancer have been hampered by various factors including (1) restricted access to tissues, (2) difficulties in propagating premalignant lesions and primary prostate tumors in vitro, and (3) limited availability of prostate cell lines for in vitro studies. There is no commercially available pair of non-malignant and tumor cells derived from the same prostate cancer patient. Primary prostate epithelial cells grow for a finite life span and then senesce. Immortalization is defined by continuous growth of otherwise senescing cells and is believed to represent an early stage in tumor progression. To examine these early stages, we have developed in vitro models of prostate epithelial cell immortalization. Generation of human primary epithelial (HPE) cells has been achieved using the serum-free keratinocyte growth medium. Retrovirus containing human telomerase reverse transcriptase (hTERT) was also used for the generation of primary non-malignant and malignant tumor cells. In addition, we have established the first immortalized cell lines of a pair of non-malignant and malignant tumors derived from an African American prostate cancer patient. Interestingly, we have found that the Rock inhibitor and feeder cells induced the conditioned reprogramming (CR) of epithelial cells—normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro, without transduction of viral or cellular genes. More recently, using CR, we have established normal and tumor cultures respectively from a patient prostatectomy. These CR cells grow indefinitely in vitro and retain stable karyology. The tumor-derived CR cells produced tumors in SCID mice. The use of novel pair of non-malignant and malignant tumor cells derived from the same patient provides a unique in vitro model for studies of early prostate cancer and for testing preventive and therapeutic regimens.

Keywords

Prostate cancer In vitro models hTERT HPV-16 E6E7 Rock inhibitor Feeder cells 

Notes

Acknowledgments

This work was funded by grants from the US Army Medical Research and Material Commend and also supported by Department of Defense Prostate Cancer Research Program (PCO30694 and PCO4252).

References

  1. 1.
    Rhim, J. S. (2013). Human prostate epithelial cell cultures. Methods in Molecular Biology, 946, 383–393.CrossRefGoogle Scholar
  2. 2.
    Burrows, M. T., Burns, J., Suzuki, Y., et al. (1917). Studies on the growth of cells. The cultivation of bladder and prostate tumors outside the body. The Journal of Urology, 1, 3–15.CrossRefGoogle Scholar
  3. 3.
    Gu, Y., Li, H., Kim, K. H., et al. (2006). Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines. Experimental Cell Research, 312, 831–843.CrossRefGoogle Scholar
  4. 4.
    Miki, J., Furusato, B., Li, H., et al. (2007). Identification of prostate stem cell markers, CD133 and CXCR4 in hTERT-immortalized primary epithelial cell lines and in prostate cancer specimens. Cancer Research, 67, 3153–3161.CrossRefGoogle Scholar
  5. 5.
    Siegel, R. L., Miller, K. D., & Jemal, A. (2015). Cancer statics 2015. CA: A Cancer Journal for Clinicians, 65, 5–29.Google Scholar
  6. 6.
    Moul, J. W. (2000). Screening for prostate cancer in African American. Current Urology Reports, 1, 57–64.CrossRefGoogle Scholar
  7. 7.
    Novone, N. M., Olive, M., Ozen, M., et al. (1997). Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clinical Cancer Research, 3, 2493–2500.Google Scholar
  8. 8.
    Koochekpour, S., Maresh, G. A., Katrner, A., et al. (2004). Establishment and characterization of a primary androgen-responsive African American prostate cancer cell line, E006AA. Prostate, 60, 141–152.CrossRefGoogle Scholar
  9. 9.
    Koochekpour, S., Willard, S. S., Shourideh, M., et al. (2014). Establishment and characterization of a highly tumorigenic African American prostate cancer cell line, E006AA-hT. International Journal of Biological Sciences, 10, 834–845.CrossRefGoogle Scholar
  10. 10.
    Theodore, S., Sharp, S., Zhou, J., et al. (2010). Establishment and characterization of a pair of non-malignant and malignant tumor-derived cell lines from an African American prostate cancer patient. International Journal of Oncology, 37, 1477–1482.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Cher, M. L., Lewis, P. E., Banerjee, M., et al. (1998). A similar pattern of chromosomal alterations in prostate cancer from African-American and Caucasian American. Clinical Cancer Research, 4, 1273–1278.PubMedGoogle Scholar
  12. 12.
    Yasunaga, Y., Nakamura, K., Ewing, C. M., et al. (2001). A novel human cell culture model for the study of familial prostate cancer. Cancer Research, 61, 5969–5973.PubMedGoogle Scholar
  13. 13.
    Smith, I. R., Freije, D., Carpten, J. D., et al. (1996). Major susceptibility locus for prostate cancer on Chromosome 1 suggested by a genome-wide search. Science, 274, 1371–1374.CrossRefGoogle Scholar
  14. 14.
    Ko, D., Gu, Y., Yasunaga, Y., et al. (2003). A novel neoplastic primary-derived human prostate epithelial cell line. International Journal of Oncology, 22, 1311–1317.PubMedGoogle Scholar
  15. 15.
    Carter, B. S., Carter, H. B., Isaacs, J. T., et al. (1990). Epidemiologic evidence regarding predisposing factors to prostate cancer. Prostate, 16, 187–197.CrossRefGoogle Scholar
  16. 16.
    Kunimi, K., Bergerheim, U. S., & Larsson, I. I. (1991). Allelotyping of human prostate adenocarcinoma. Genomics, 11, 530–536.CrossRefGoogle Scholar
  17. 17.
    Taylor-Papadimitriou, J., Sheaver, M., & Stoker, M. G. (1977). Growth requirements of human mammary epithelial cells in culture. International Journal of Cancer, 20, 903–908.CrossRefGoogle Scholar
  18. 18.
    Bartek, J., Barikova, J., Kyprianon, N., et al. (1991). Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus. Proceedings of the National Academy of Sciences of the United States of America, 88, 3520–3524.CrossRefGoogle Scholar
  19. 19.
    Meiser, L. F., Wu, S. Q., Christian, B. J., et al. (1988). Cytogenetic instability with balanced chromosome changes in an SV40 transformed human uroepithelial cell line. Cancer Research, 48, 3215–3220.Google Scholar
  20. 20.
    Foster, S. A., & Galloway, D. A. (1996). Human papillomavirus type E7 alleviates a proliferation block in early passage human mammary epithelial cells. Oncogene, 12, 1773–1779.PubMedGoogle Scholar
  21. 21.
    Counter, C. M., Hahn, W. C., Wei, W., et al. (1998). Dissociation among in vitro telomerase activity, telerase maintenance and cellular immortalization. Proceedings of the National Academy of Sciences of the United States of America, 95, 147234–114728.CrossRefGoogle Scholar
  22. 22.
    Claassen, D. A., Dester, M. M., & Rizzino, A. (2009). ROCK inhibition enhances the recovery and growth of cryopreserved human embryonic stem cells and human induced pluripotent stem cells. Molecular Reproduction and Development, 76, 722–732.CrossRefGoogle Scholar
  23. 23.
    Liu, X., Ory, V., Chapman, S., et al. (2012). ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. The American Journal of Pathology, 180, 599–607.CrossRefGoogle Scholar
  24. 24.
    Suprynowicz, F. A., Upadhyay, G., Krawczyk, E., et al. (2012). Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 109, 20035–20040.CrossRefGoogle Scholar
  25. 25.
    Saenz, F. R., Ory, V., Alotaiby, M., et al. (2014). Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype. PLoS One, 9(5), e97666.CrossRefGoogle Scholar
  26. 26.
    Liu, X., Dakio, A., Chan, R., et al. (2008). Cell-restricted immortalization by human papillomavirus correlated telomerase activation and engagement of the hTERT promotor by Myc. Journal of Virology, 82, 11568–11576.CrossRefGoogle Scholar
  27. 27.
    Kiyono, T., Foster, S. A., Koop, J. A., et al. (1998). Both Rb/p16/NK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature, 396, 84–88.CrossRefGoogle Scholar
  28. 28.
    Liu, X., Dakie, C., Zhang, Y., et al. (2009). HPV E6 protein interacts physically and functionally with the cellular telomeres complex. Proceedings of the National Academy of Sciences of the United States of America, 106, 18780–18785.CrossRefGoogle Scholar
  29. 29.
    Yue, J., Shukla, R., Accardi, R., et al. (2011). HPV18 E7 regulate action cytokelaton structure for increasing cell proliferation through CK2 and the eukaryotic elongation factor1A. Journal of Virology, 85, 8477–8494.CrossRefGoogle Scholar
  30. 30.
    Charette, S. T., & McCance, D. J. (2007). The E7 protein from human papillomavirus type 16 enhances keratinocyte migration in Akt-dependent manner. Oncogene, 26, 7386–7390.CrossRefGoogle Scholar
  31. 31.
    Timofeeva, O. A., Palechon-Ceron, N., Li, G., et al. (2017). Conditionally reprogrammed normal and primary tumor prostate epithelial cells: A novel patient-derived cell model for studies of human prostate cancer. Oncotarget, 8, 22741–22758.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Johng S. Rhim
    • 1
  1. 1.Department of SurgeryUniformed Services University of the Health SciencesBethesdaUSA

Personalised recommendations