title: Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents.
abstract: Despite advances in diagnosis and treatment of prostate cancer, development of metastases remains a major clinical challenge. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Identification of proteins that inhibit dissemination of cancer cells will provide new perspectives to define novel therapeutics. Development of antimetastatic drugs that trigger or mimic the effect of metastasis suppressors represents new therapeutic approaches to improve patient survival. This review focuses on different biochemical and cellular functions of metastasis suppressors known to play a role in prostate carcinogenesis and progression. Ten putative metastasis suppressors implicated in prostate cancer are discussed. CD44s is decreased in both PIN and cancer; Drg-1, E-cadherin, KAI-1, RKIP, and SSeCKS show similar expression between benign epithelia and PIN, but are downregulated in invasive cancer; whereas, maspin, MKK4, Nm23 and PTEN are upregulated in PIN and downregulated in cancer. Moreover, the potential role of microRNA in prostate cancer progression, the understanding of the cellular distribution and localization of metastasis suppressors, their mechanism of action, their effect on prostate invasion and metastasis, and their potential use as therapeutics are addressed.
authors.affiliation: Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4390, USA.
authors.forename: Zahraa I
authors.initials: ZI
authors.lastname: Khamis
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Iczkowski
authors.forename: Qing-Xiang Amy
authors.initials: QX
authors.lastname: Sang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins