Arreygue-Garcia Naela A, Daneri-Navarro Adrian, del Toro-Arreola Alicia, Cid-Arregui Angel, Gonzalez-Ramella Oscar, Jave-Suarez Luis F, Aguilar-Lemarroy Adriana, Troyo-Sanroman Rogelio, Bravo-Cuellar Alejandro, Delgado-Rizo Vidal, Garcia-Iglesias Trinidad, Hernandez-Flores Georgina, Del Toro-Arreola Susana
Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
BMC Cancer. 2008 Jan 21;8:16. doi: 10.1186/1471-2407-8-16.
Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors.
Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion.
Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells.
Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells.
宫颈癌是全球女性中第二常见的癌症。自然杀伤细胞(NK)和细胞毒性T细胞通过NKG2D激活受体在清除病毒感染细胞和肿瘤细胞中发挥重要作用,该受体可通过与主要组织相容性复合体I类相关链A(MICA)蛋白结合来促进靶细胞的裂解。上皮肿瘤患者血清中MICA水平升高。本研究的目的是比较宫颈癌或癌前病变患者与健康供者血液样本中可溶性MICA(sMICA)水平以及表达NKG2D的NK细胞和T细胞水平。
分别采集含或不含肝素的外周血以获得单核细胞或血清。通过酶联免疫吸附测定(ELISA)测量血清sMICA水平,并通过流式细胞术分析表达NKG2D的免疫细胞。此外,进行相关性分析以将sMICA水平与NKG2D表达或病变阶段相关联。
几乎所有患者的血清中都检测到大量sMICA。我们发现与健康供者相比,宫颈癌组和病变组中表达NKG2D的NK细胞和T细胞数量均减少。Pearson分析显示sMICA与表达NKG2D的T细胞之间呈负相关;然而,当将该分析应用于NK细胞上的sMICA和NKG2D表达时,我们未发现显著相关性。
我们的结果首次表明,与健康供者相比,宫颈癌和癌前病变患者的血清中sMICA水平较高。我们还观察到患者样本中表达NKG2D的NK细胞和T细胞数量减少;然而,仅在T细胞中观察到sMICA与NKG2D表达之间存在显著负相关。