Bolenz C, Martini T, Michel M S
Klinik für Urologie, Universitätsmedizin Mannheim, Fakultät für Medizin der Universität Heidelberg, Theodor-Kutzer-Ufer 1, 68167, Mannheim, Deutschland,
Urologe A. 2013 Sep;52(9):1242-7. doi: 10.1007/s00120-013-3309-z.
Local invasion of cancer cells occurs early during the progression of urothelial carcinoma. Micrometastatic disease and the presence of nodal metastases are major causes of cancer-specific mortality following radical surgery. Only surrogate markers for aggressive and micrometastatic disease have been identified. The metastatic cascade is complex, including multiple steps from initial invasion to colonization and proliferation at distant sites. The initial mechanisms of cancer cell dissemination in urothelial carcinoma are poorly understood. Various proteases, chemokines and growth factors are involved in this process and alterations of the lymphatic system may promote systemic spread. There is a high demand for therapeutic targeting of the metastatic process. Functional preclinical studies in representative models are therefore required to better elucidate the multiple steps of progression. We review the current knowledge on factors associated with metastasis in urothelial carcinoma. Preclinical approaches to identify key player molecules for invasion and to develop new therapeutic strategies are discussed.
癌细胞的局部浸润在尿路上皮癌进展的早期就会发生。微转移疾病和淋巴结转移的存在是根治性手术后癌症特异性死亡的主要原因。目前仅确定了侵袭性和微转移疾病的替代标志物。转移级联反应很复杂,包括从最初的侵袭到远处部位的定植和增殖的多个步骤。尿路上皮癌中癌细胞播散的初始机制尚不清楚。各种蛋白酶、趋化因子和生长因子都参与了这一过程,而淋巴系统的改变可能会促进全身扩散。对转移过程进行治疗性靶向的需求很高。因此,需要在代表性模型中进行功能性临床前研究,以更好地阐明进展的多个步骤。我们综述了目前关于尿路上皮癌转移相关因素的知识。讨论了识别侵袭关键分子和开发新治疗策略的临床前方法。