MOLECULAR INSIGHTS INTO PROSTATE CANCER PROGRESSION: THE MISSING LINK OF TUMOR MICROENVIRONMENT

No AccessJournal of UrologyReview Articles1 Jan 2005MOLECULAR INSIGHTS INTO PROSTATE CANCER PROGRESSION: THE MISSING LINK OF TUMOR MICROENVIRONMENT LELAND W.K. CHUNG, ADAM BASEMAN, VASILY ASSIKIS, and HAIYEN E. ZHAU LELAND W.K. CHUNGLELAND W.K. CHUNG More articles by this author , ADAM BASEMANADAM BASEMAN More articles by this author , VASILY ASSIKISVASILY ASSIKIS More articles by this author , and HAIYEN E. ZHAUHAIYEN E. ZHAU More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000141582.15218.10AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Tumor cell genotype and phenotype have been considered the only determinants supporting cancer growth and metastasis. This review focuses on the published literature that suggests that tumor-microenvironment interaction has a decisive role in controlling local cancer growth, invasion and distant metastasis. As this review shows, genetic alterations in prostate cancer cells alone are not enough to confer metastatic status without a supporting tumor microenvironment. Effective therapeutic targeting requires a deeper understanding of the interplay between tumor and stroma. Approaches co-targeting tumor and stroma already show promise over the conventional targeting of tumor cells alone in preventing prostate cancer progression and eradicating preexisting or newly developed prostate cancers in bone and visceral organs. Materials and Methods: A literature survey using the MEDLINE database was performed in basic and clinical publications relevant to tumor-host microenvironment interaction. Information pertinent to the biology and therapy of prostate cancer local growth and distant metastases was specifically emphasized. Results: Tumor associated stroma actively fuel the progression of prostate cancer from localized growth to the invasion of surrounding tissues, and the development of distant bone and visceral organ metastasis. In concert with this progression tumor cells recovered from metastatic sites could represent a subpopulation of preexisting tumor cells or could be a newly acquired variant subsequent to tumor-stromal interaction. Experimental data from our laboratory and others suggest that permanent genetic and phenotypic changes occur in prostate cancer cells after 3-dimensional co-culture in vitro or when co-inoculated and grown with inductive stromal cells in vivo. These results support the idea that newly acquired variants are the dominant mechanism of prostate cancer progression. Intercellular communication between prostate cancer cells and organ specific stroma, including prostate and marrow stroma, could involve diffusible soluble and solid matrix molecules as mediators, leading to the development of metastasis. This presents a new opportunity for therapeutic targeting for the treatment of benign and malignant growth of the prostate glands. This review summarizes specific research implicating tumor-microenvironment interaction as the molecular basis of cancer progression, providing a rationale for targeting tumor and the tumor associated microenvironment in the management of androgen independent and bone metastatic prostate cancer progression in patients. Conclusions: Cancer is not a single cell disease. Aberrant cancer cells and their interactive microenvironment are needed for prostate cancer to progress to androgen independence and distant metastasis. It is highly plausible that newly evolved prostate cancer cell clones dominate cancer metastasis after cell-cell and cell-matrix interaction with the host microenvironment, rather than the selection or expansion of a preexisting prostate cancer cell clone(s). Based on this premise potential molecular targets in the microenvironment are especially emphasized. Further elucidation of the molecular mechanisms underlying tumor-stromal interaction may yield improved medical treatments for prostate cancer growth and metastasis. References 1 : The distribution of secondary growths in cancer of the breast. Lancet1889; 1: 571. Google Scholar 2 : Clonal dominance of primary tumours by metastatic cells: genetic analysis and biological implications. Cancer Surv1988; 7: 597. Google Scholar 3 : The pathogenesis of cancer metastasis. Nature1980; 283: 139. Google Scholar 4 : In vitro properties of human melanoma cells metastatic in nude mice. Cancer Res1990; 50: 2296. 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Google Scholar From the Departments of Urology (LWKC, AB, HEZ) and Medical Oncology (VA), Emory University School of Medicine, Atlanta, Georgia© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByAtala A (2020) Re: The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer Metastasis by Coordinating Stemness and Immune SuppressionJournal of Urology, VOL. 203, NO. 4, (665-666), Online publication date: 1-Apr-2020.Atala A (2019) Re: Alterations of Tumor Microenvironment by Nitric Oxide Impedes Castration-Resistant Prostate Cancer GrowthJournal of Urology, VOL. 202, NO. 1, (35-36), Online publication date: 1-Jul-2019.Atala A (2018) Re: An Aberrant SREBP-Dependent Lipogenic Program Promotes Metastatic Prostate CancerJournal of Urology, VOL. 200, NO. 3, (501-502), Online publication date: 1-Sep-2018.Atala A (2018) Re: Mesenchymal Stem Cells are Recruited and Activated into Carcinoma-Associated Fibroblasts by Prostate Cancer Microenvironment-Derived TGF-β1Journal of Urology, VOL. 196, NO. 6, (1817-1817), Online publication date: 1-Dec-2016. Volume 173Issue 1January 2005Page: 10-20 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordsneoplasm metastasisprostatic neoplasmsprostategrowth substancesdisease progressionMetricsAuthor Information LELAND W.K. CHUNG More articles by this author ADAM BASEMAN More articles by this author VASILY ASSIKIS More articles by this author HAIYEN E. ZHAU More articles by this author Expand All Advertisement PDF DownloadLoading ...