Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents. Med Res Rev 2012 Sep;32(5):1026-77
Date
08/14/2012Pubmed ID
22886631DOI
10.1002/med.20232Scopus ID
2-s2.0-84864837159 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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.
Author List
Khamis ZI, Iczkowski KA, Sang QXMESH terms used to index this publication - Major topics in bold
AnimalsDisease Models, Animal
Humans
Male
Neoplasm Invasiveness
Neoplasm Metastasis
Prostatic Intraepithelial Neoplasia
Prostatic Neoplasms
Tumor Suppressor Proteins