Genetic and microenvironmental implications in prostate cancer progression and metastasis.
Prometastatic gene expression events occur during the early phases of prostate oncogenesis, even though overlaping with genes that induce primary cancer growth. Cytogenetic and genomic profiling analyses have identified many cancer-associated chromosomal abnormalities consisting mainly in losses in the early phases of sporadic primary prostate carcinoma. Metastatic genes are those in which gains in oncogene functional activity or lack of tumor suppressor genes enable cancer cells to detach, escape into the circulation, penetrate and colonize distant organs. In metastatic prostate carcinoma some genes, such as MTA1 and MYBL2, are differentially upregulated in comparison to primary site, while IGFBP, DAN1, FAT and RAB5A appear to be downregulated. Epigenetic alterations, such as histone deacetylation/hypermethylation, are also involved in the metastasis promotion. Nevertheless, during oncogenesis and cancer progression, prostate cancer cells may regain pluripotent stem cell-like properties or, as an alternative, may be, them selves, malignant stem cell clones, equipped with self-renewal mechanisms. Pleiotropic contributions to cancer progression and metastatic spread are also brought up from a variety of tumor microenvironment-associated factors. Moreover, inflammatory processes can partecipate in prostate tumorigenesis and cancer progression through several mechanisms, such as generation of both oxygen and nitrogen reactive species, induction of cyclooxygenase-2 and production of growth factors and cytokines by neutrophils and macrophages of host microenvironment. The knowledge of both genetic and microenvironmental cancer aggressiveness factors is necessary to define timing and suitability of therapeutical strategies.
Alberti
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L.D. of Surgical Semeiotics, University of Parma, Parma, Italy.
D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000150:complications; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*