[Invasion patterns and metastasis of urothelial carcinoma. A challenge for translational research]

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.