New targets for therapy in prostate cancer

Modulation of stromal-epithelial interactions

Leland W K Chung, Chia Ling Hsieh, Andrew Law, Shian Ying Sung, Thomas Gardner, Masayuki Egawa, Shigeji Matsubara, Haiyen E. Zhau

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Changes in genomic and phenotypic expression of progressing prostate tumors and their stroma occur in a dynamic fashion based on bidirectional signaling from stromal-epithelial interactions. These interactions may underlie the ability of prostate cancer cells to survive and proliferate in the prostate and bone. By investigating the phenotypic and genotypic changes of stromal cells adjacent to cancer cells and the reciprocal changes of cancer cells, novel molecular markers may be developed to diagnose cancer earlier before pathologic appearance of cancer cells at the primary site. Attacking epithelial and stromal elements together is a unique approach to both localized and metastatic prostate cancer therapy. Co-targeting both tumor cells and stroma requires identifying a reliable tumor and tissue-specific cis-DNA element, such as osteocalcin (OC) promoter. OC expression is elevated in prostate tumor cells and in prostate and bone stromal cells interdigitating with both localized and metastatic prostate epithelium. We have previously designed an adenovirus-based therapeutic gene vehicle and demonstrated that a replication-competent adenoviral vector (Ad vector) is highly efficient in blocking the growth of cancer cells in culture, including cells without androgen receptor as well as cells that do or do not make prostate-specific antigen. In vivo, intravenous administration of an Ad-OC vector was effective against preexisting human prostate cancer subcutaneous and bone xenografts. The addition of vitamin D 3 enhanced further viral replication at target sites. Co-targeting tumor cells and stroma using systemic Ad vector is a viable and promising option for treatment of both localized and metastatic prostate cancer.

Original languageEnglish
Pages (from-to)44-54
Number of pages11
JournalUrology
Volume62
Issue number5 SUPPL. 1
DOIs
StatePublished - Nov 2003

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Prostatic Neoplasms
Prostate
Neoplasms
Osteocalcin
Therapeutics
Stromal Cells
Bone and Bones
Bone Neoplasms
Cholecalciferol
Androgen Receptors
Prostate-Specific Antigen
Early Detection of Cancer
Heterografts
Adenoviridae
Intravenous Administration
Epithelium
Cell Culture Techniques
DNA
Growth
Genes

ASJC Scopus subject areas

  • Urology

Cite this

Chung, L. W. K., Hsieh, C. L., Law, A., Sung, S. Y., Gardner, T., Egawa, M., ... Zhau, H. E. (2003). New targets for therapy in prostate cancer: Modulation of stromal-epithelial interactions. Urology, 62(5 SUPPL. 1), 44-54. https://doi.org/10.1016/S0090-4295(03)00796-9

New targets for therapy in prostate cancer : Modulation of stromal-epithelial interactions. / Chung, Leland W K; Hsieh, Chia Ling; Law, Andrew; Sung, Shian Ying; Gardner, Thomas; Egawa, Masayuki; Matsubara, Shigeji; Zhau, Haiyen E.

In: Urology, Vol. 62, No. 5 SUPPL. 1, 11.2003, p. 44-54.

Research output: Contribution to journalArticle

Chung, LWK, Hsieh, CL, Law, A, Sung, SY, Gardner, T, Egawa, M, Matsubara, S & Zhau, HE 2003, 'New targets for therapy in prostate cancer: Modulation of stromal-epithelial interactions', Urology, vol. 62, no. 5 SUPPL. 1, pp. 44-54. https://doi.org/10.1016/S0090-4295(03)00796-9
Chung, Leland W K ; Hsieh, Chia Ling ; Law, Andrew ; Sung, Shian Ying ; Gardner, Thomas ; Egawa, Masayuki ; Matsubara, Shigeji ; Zhau, Haiyen E. / New targets for therapy in prostate cancer : Modulation of stromal-epithelial interactions. In: Urology. 2003 ; Vol. 62, No. 5 SUPPL. 1. pp. 44-54.
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