Antonioli Luca, Haskó György, Fornai Matteo, Colucci Rocchina, Blandizzi Corrado
University of Pisa, Department of Clinical and Experimental Medicine , Via Roma 55, 56126 - Pisa , Italy +39 050 2218762 ; +39 050 2218758 ;
Expert Opin Ther Targets. 2014 Sep;18(9):973-7. doi: 10.1517/14728222.2014.925883. Epub 2014 Jun 24.
Increasing evidence supports the occurrence of an intriguing link between tumor onset and development with the microenvironment in which cancer cells are embedded. In this context, a critical role of CD73, in calibrating the duration, magnitude and composition of adenosine signaling in cancer development and progression, has been identified. Adenosine levels are increased in cancer tissues as the result of genetic alterations that occur during tumor progression. Indeed, a rearrangement of the adenosine metabolic machinery has been described within the neoplastic milieu with the aim of amplifying adenosine generation, thereby creating an immune tolerant microenvironment suitable for tumor onset and development. At the same time, adenosine, through the engagement of receptors expressed on neoplastic cells, finely tunes the growth and dissemination of tumor mass, thus interfering with cancer proliferation, apoptosis and metastasis. Based on current knowledge, an improved understanding of how and to what extent adenosine participates to the molecular mechanisms underlying cancer development and diffusion will pave the way toward new therapeutic advances. The discovery and development of drugs targeted on this system might lead to substantial improvements in the clinical management of various cancers.
越来越多的证据支持肿瘤的发生和发展与癌细胞所处的微环境之间存在着一种有趣的联系。在这种情况下，已确定CD73在调节癌症发生和发展过程中腺苷信号的持续时间、强度和组成方面起着关键作用。由于肿瘤进展过程中发生的基因改变，癌症组织中的腺苷水平会升高。事实上，在肿瘤微环境中已经描述了腺苷代谢机制的重新排列，目的是放大腺苷的产生，从而创造一个适合肿瘤发生和发展的免疫耐受微环境。同时，腺苷通过与肿瘤细胞上表达的受体结合，精细地调节肿瘤块的生长和扩散，从而干扰癌症的增殖、凋亡和转移。基于目前的知识，更好地理解腺苷如何以及在多大程度上参与癌症发生和扩散的分子机制将为新的治疗进展铺平道路。针对该系统的药物的发现和开发可能会显著改善各种癌症的临床管理。
