Prostate tumor-stroma interaction: Molecular mechanisms and opportunities for therapeutic targeting

Shian Ying Sung, Leland W K Chung

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Maintenance of cell and tissue homeostasis is dependent upon the dynamic balance of cell proliferation, differentiation, and apoptosis through interactions between cells and their microenvironment. The unique prostatic cellular phenotypes are induced and maintained by interaction between epithelium and adjacent stroma through intimate intercellular signaling pathways. In this article, we summarize current advances in the tumor-stroma interaction and its biologic and therapeutic implications. We specifically emphasize current studies of the possible factors driving the "vicious cycle" between stroma and emerging prostate tumor epithelial cells that may be responsible for carcinogenesis and metastasis to bone. Stroma responds both genotypically and phenotypically to tumor epithelium upon co-culture under 3-D conditions. Likewise, the emerging carcinoma responds to stromal signals that drive progression to malignancy. A vicious cycle mediated by soluble and insoluble molecules secreted by tumor cells and stroma appear be the critical factors supporting and sustaining tumor colonization in bone. Co-targeting tumor and stroma with therapeutic agents has yielded promising results both in pre-clinical models of prostate cancer and bony metastasis and in clinical trials of patients treated with a dual tumor and stroma targeting strategies. In conclusion, understanding and targeting the interaction of the tumor and its stromal microenvironmant may improve the prognosis, reduce the suffering and increase the survival of patients with advanced cancer metastasis.

Original languageEnglish
Pages (from-to)506-521
Number of pages16
JournalDifferentiation
Volume70
Issue number9-10
DOIs
Publication statusPublished - Dec 2002
Externally publishedYes

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Keywords

  • Bone metastasis
  • Cytokine
  • Extracellular matrix (ECM)
  • Molecular targeting
  • Prostate cancer
  • Stromalepithelial interaction
  • Vicious cycle

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Developmental Biology
  • Cell Biology

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