Stark Timothy, Livas Lydia, Kyprianou Natasha
1 Department of Urology, 2 Department of Molecular Biochemistry, 3 Department of Pathology, 4 The Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Transl Androl Urol. 2015 Aug;4(4):455-63. doi: 10.3978/j.issn.2223-4683.2015.04.12.
Chronic inflammation contributes to the onset and progression of human cancer, via modifications in the tumor microenvironment by remodeling the extracellular matrix (ECM) and initiating epithelial mesenchymal transition (EMT). At the biological level, chronically inflamed cells release cytokines that are functionally dictating a constitutively active stroma, promoting tumor growth and metastasis. In prostate cancer, inflammation correlates with increased development of "risk factor" lesions or proliferative inflammatory atrophy (PIA). Chronic inflammation in benign prostate biopsy specimens can be associated with high-grade prostate tumors in adjacent areas. In this article, we discuss the current understanding of the incidence of inflammation in prostate cancer progression and the significance of the process in therapeutic targeting of specific inflammatory signaling pathways and critical effectors during tumor progression. Further understanding of the process of chronic inflammation in prostate tumor progression to metastasis will enable development and optimization of novel therapeutic modalities for the treatment of high-risk patients with advanced disease.
慢性炎症通过重塑细胞外基质(ECM)和启动上皮-间质转化(EMT)来改变肿瘤微环境,从而促进人类癌症的发生和发展。在生物学层面,慢性炎症细胞释放的细胞因子可使基质持续处于激活状态,进而促进肿瘤生长和转移。在前列腺癌中,炎症与“危险因素”病变或增殖性炎性萎缩(PIA)的发生增加相关。良性前列腺活检标本中的慢性炎症可能与相邻区域的高级别前列腺肿瘤有关。在本文中,我们讨论了目前对炎症在前列腺癌进展中的发生率的理解,以及该过程在肿瘤进展期间针对特定炎症信号通路和关键效应器进行治疗靶向的意义。进一步了解前列腺肿瘤进展至转移过程中的慢性炎症,将有助于开发和优化针对晚期高危患者的新型治疗方法。