Albertó Marina, Cuello Hector Adrián, Gulino Cynthia Anabella, Pifano Marina, Belgorosky Denise, Gabri Mariano Rolando, Eiján Ana María, Segatori Valeria Inés
Laboratory of Molecular Oncology, Quilmes National University, Bernal B1876BXD, Argentina.
Research Area, Instituto de Oncología Angel H. Roffo, Universidad de Buenos Aires, Buenos Aires 1417 DTB, Argentina.
Oncol Lett. 2019 Mar;17(3):3141-3150. doi: 10.3892/ol.2019.9995. Epub 2019 Jan 31.
The characterization of murine cell lines is of great importance in order to identify preclinical models that could resemble human diseases. Aberrant glycosylation includes the loss, excessive or novel expression of glycans and the appearance of truncated structures. MB49 and MB49-I are currently the only two murine cell lines available for the development of preclinical bladder cancer models. The glycans Lewis X (LeX), Sialyl lewis X (SLeX) and Sialyl Tn (STn) have previously been associated with aggressiveness, dissemination and poor prognosis in human bladder cancer, additionally N-glycolyl GM3 (NGcGM3) is a neo-antigen expressed in many types of tumors; however, to the best of our knowledge, its expression has not previously been assessed in this type of cancer. Taking into account the relevance of glycans in tumor biology and considering that they can act as targets of therapies and biomarkers, the present study evaluated the expression of LeX, SLeX, STn and NGcGM3 in MB49 and MB49-I cells, in different growth conditions such as monolayer cultures, three-dimensional multicellular spheroids and mouse heterotopic and orthotopic tumors. The expression of LeX was not detected in either cell line, whereas SLeX was expressed in monolayers, spheroids and orthotopic tumors of both cell lines. STn was only identified in MB49 monolayers and spheroids. There are no reports concerning the expression of NGcGM3 in human or murine bladder cancer. In our hands, MB49 and MB49-I expressed this ganglioside in all the growth conditions evaluated. The assessment of its expression in cancer cell lines and patient tumors is of great importance, considering the relevance of this ganglioside in tumor biology. The data obtained by the present study demonstrates that glycan expression may be substantially altered depending on the growth conditions, highlighting the importance of the characterization of murine cancer models. To the best of our knowledge, the present study is the first to examine the expression of cancer-associated glycans, in the two murine cell lines available for the development of preclinical studies in bladder cancer.
为了识别可能类似于人类疾病的临床前模型，对小鼠细胞系进行表征非常重要。异常糖基化包括聚糖的缺失、过度表达或新表达以及截短结构的出现。MB49和MB49-I是目前仅有的两种可用于开发临床前膀胱癌模型的小鼠细胞系。聚糖Lewis X（LeX）、唾液酸化Lewis X（SLeX）和唾液酸化Tn（STn）先前已与人膀胱癌的侵袭性、扩散和不良预后相关，此外，N-糖基化神经节苷脂GM3（NGcGM3）是在多种肿瘤中表达的一种新抗原；然而，据我们所知，其在这类癌症中的表达此前尚未得到评估。考虑到聚糖在肿瘤生物学中的相关性，并鉴于它们可作为治疗靶点和生物标志物，本研究评估了LeX、SLeX、STn和NGcGM3在MB49和MB49-I细胞中的表达，这些细胞处于不同的生长条件下，如单层培养、三维多细胞球体以及小鼠异位和原位肿瘤。在这两种细胞系中均未检测到LeX的表达，而SLeX在两种细胞系的单层、球体和原位肿瘤中均有表达。STn仅在MB49的单层和球体中被鉴定出来。目前尚无关于NGcGM3在人或小鼠膀胱癌中表达的报道。在我们的研究中，MB49和MB49-I在所有评估的生长条件下均表达这种神经节苷脂。考虑到这种神经节苷脂在肿瘤生物学中的相关性，评估其在癌细胞系和患者肿瘤中的表达非常重要。本研究获得的数据表明，聚糖表达可能会根据生长条件而发生显著变化，这凸显了对小鼠癌症模型进行表征的重要性。据我们所知，本研究是首次在可用于膀胱癌临床前研究的两种小鼠细胞系中检测癌症相关聚糖的表达。
