Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, U.S.A.
Anticancer Res. 2020 Dec;40(12):6613-6621. doi: 10.21873/anticanres.14686. Epub 2020 Dec 7.
BACKGROUND/AIM: Cancer stem cells (CSCs) are a subpopulation of cells that retain self-renewal and pluripotency capabilities, are resistant to chemotherapy, and are thought to facilitate metastasis. Target cell expression of proliferating cell nuclear antigen (PCNA) or lectin-like transcript 1 (LLT1) inhibits natural killer (NK) cell functions. The purpose of this study was to characterize the expression of LLT1 or PCNA as NK cell evasion strategies of HCT 116, a colorectal cancer cell line.
Protein expression was determined by flow cytometry and/or confocal microscopy. Stem-like cells were sorted and characterized, and NK cell effector functions measured by interferon-γ secretion and cytotoxicity assay.
PCNA expressing cells are potential CSCs, blocking PCNA alters interferon-γ secretion, and blocking PCNA or LLT1 increases cytotoxicity.
PCNA is a potential biomarker of stem-like colon cancer cells. Based on the results of this study, PCNA and LLT1 should be further explored as in vivo immunotherapeutic targets for NK cell-mediated killing.
背景/目的：癌症干细胞（CSCs）是一种能够自我更新和保持多能性的细胞亚群，对化疗具有耐药性，并被认为促进了转移。增殖细胞核抗原（PCNA）或凝集素样转录本 1（LLT1）在靶细胞中的表达抑制自然杀伤（NK）细胞的功能。本研究的目的是描述 HCT 116（一种结直肠癌细胞系）中 LLT1 或 PCNA 的表达作为 NK 细胞逃避策略。
通过流式细胞术和/或共聚焦显微镜确定蛋白表达。分选和表征类干细胞，并通过干扰素-γ分泌和细胞毒性测定来测量 NK 细胞的效应功能。
表达 PCNA 的细胞是潜在的 CSCs，阻断 PCNA 会改变干扰素-γ的分泌，而阻断 PCNA 或 LLT1 会增加细胞毒性。
PCNA 是结直肠癌细胞类干细胞的潜在生物标志物。基于这项研究的结果，PCNA 和 LLT1 应该进一步作为 NK 细胞介导杀伤的体内免疫治疗靶点进行探索。
