Apoptosis, Immunity & Cancer Group, Department of Biochemistry and Molecular and Cell Biology, Faculty of Sciences, University of Zaragoza and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.
Department of Human Anatomy and Histology, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain.
Cancer Treat Res Commun. 2021;27:100355. doi: 10.1016/j.ctarc.2021.100355. Epub 2021 Mar 19.
9-kDa granulysin is a protein expressed into the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It has been shown to exert cytolysis on microbes and tumors. We showed previously that 9-kDa granulysin exerted cell death by apoptosis in vitro on hematological tumor cell lines and also on cells from B-cell chronic lymphocytic leukemia (B-CLL) patients. In addition, we have shown the anti-tumor efficiency of granulysin as a single agent in two in vivo models of human tumor development in athymic mice, the MDA-MB-231 mammary adenocarcinoma and the NCI-H929 multiple myeloma, without signs of overt secondary effects by itself. In this work, we have tested recombinant 9-kDa granulysin in an in vivo and especially aggressive model of melanoma development, xenografted UACC62 cells in athymic mice. Recombinant granulysin was administered once UACC62-derived tumors were detectable and it substantially retarded the in vivo development of this aggressive tumor. We could also detect apoptosis induction and increased NK cell infiltration inside granulysin-treated tumor tissues. These observations are especially interesting given the possibility of treating melanoma by intra-tumor injection.
9-kDa 颗粒溶素是一种表达在人类细胞毒性 T 淋巴细胞 (CTL) 和自然杀伤 (NK) 细胞颗粒中的蛋白质。它已被证明对微生物和肿瘤具有细胞溶解作用。我们之前曾表明，9-kDa 颗粒溶素在体外对血液系统肿瘤细胞系以及来自 B 细胞慢性淋巴细胞白血病 (B-CLL) 患者的细胞也能通过细胞凋亡发挥细胞死亡作用。此外，我们还在裸鼠的两种人肿瘤发展的体内模型中显示了颗粒溶素作为单一药物的抗肿瘤效率，即 MDA-MB-231 乳腺腺癌和 NCI-H929 多发性骨髓瘤，没有明显的自身的副作用迹象。在这项工作中，我们在黑色素瘤发展的一种体内特别是侵袭性模型中测试了重组 9-kDa 颗粒溶素，即将 UACC62 细胞异种移植到裸鼠中。在 UACC62 衍生的肿瘤可检测到时给予重组颗粒溶素，它大大延缓了这种侵袭性肿瘤的体内发展。我们还可以检测到凋亡诱导和 NK 细胞浸润在颗粒溶素处理的肿瘤组织内增加。这些观察结果特别有趣，因为有可能通过肿瘤内注射来治疗黑色素瘤。
