Grisendi Giulia, Spano Carlotta, Rossignoli Filippo, D Souza Naomi, Golinelli Giulia, Fiori Agnese, Horwitz Edwin M, Guarneri Valentina, Piacentini Federico, Paolucci Paolo, Dominici Massimo
Laboratory of Cellular Therapy Department of Medical and Surgical Sciences for Children & Adults University-Hospital of Modena and Reggio Emilia Via del Pozzo 71, 41124 Modena, Italy.
Curr Drug Targets. 2016;17(10):1111-26. doi: 10.2174/1389450117666160307143226.
Tumor stroma (TS) plays relevant roles in all steps of cancer development. We here address several fundamental aspects related with the interaction between cancer cells and their stromal counterparts. Dissecting these players is of pivotal importance to understand oncogenesis, immunoescape and drug resistance. In addition, this better comprehension will allow the introduction of novel and more effective therapeutic approaches where manipulated stromal elements may become detrimental for tumor growth. Our group and others rely on the use of multipotent mesenchymal stromal/stem cells (MSC) as anti-cancer tools, since these putative TS cell precursors can deliver potent apoptosis-inducing agents. Multimodal-armed MSC can target a variety of cancers in vitro and, when injected in vivo, they localize into tumors mediating cell death without evident toxicities to normal tissues. While several aspects of these strategies shall require further investigations, these approaches collectively indicate how TS manipulation by MSC represents a tool to influence the fate of cancer cells, creating a new generation of anti-cancer strategies.
肿瘤基质(TS)在癌症发展的各个阶段都发挥着重要作用。我们在此探讨与癌细胞及其基质对应物之间相互作用相关的几个基本方面。剖析这些因素对于理解肿瘤发生、免疫逃逸和耐药性至关重要。此外,这种更深入的理解将有助于引入新的、更有效的治疗方法,其中对基质成分的操控可能对肿瘤生长产生不利影响。我们团队以及其他团队依赖于使用多能间充质基质/干细胞(MSC)作为抗癌工具,因为这些假定的TS细胞前体可以递送强效的凋亡诱导剂。多模式武装的MSC在体外可以靶向多种癌症,并且当注射到体内时,它们会定位于肿瘤中,介导细胞死亡,而对正常组织没有明显毒性。虽然这些策略的几个方面需要进一步研究,但这些方法共同表明,MSC对TS的操控如何成为影响癌细胞命运的一种工具,从而开创了新一代抗癌策略。