Siwowska Klaudia, Schmid Raffaella M, Cohrs Susan, Schibli Roger, Müller Cristina
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSI 5232, Switzerland.
Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, Switzerland.
Pharmaceuticals (Basel). 2017 Aug 15;10(3):72. doi: 10.3390/ph10030072.
The folate receptor (FR) is expressed in a variety of gynecological cancer types. It has been widely used for tumor targeting with folic acid conjugates of diagnostic and therapeutic probes. The cervical KB tumor cells have evolved as the standard model for preclinical investigations of folate-based (radio) conjugates. In this study, a panel of FR-expressing human cancer cell lines-including cervical (HeLa, KB, KB-V1), ovarian (IGROV-1, SKOV-3, SKOV-3.ip), choriocarcinoma (JAR, BeWo) and endometrial (EFE-184) tumor cells-was investigated in vitro and for their ability to grow as xenografts in mice. FR-expression levels were compared in vitro and in vivo and the cell lines were characterized by determination of the sensitivity towards commonly-used chemotherapeutics and the expression of two additional, relevant tumor markers, HER2 and L1-CAM. It was found that, besides KB cells, its multiresistant KB-V1 subclone as well as the ovarian cancer cell lines, IGROV-1 and SKOV-3.ip, could be used as potentially more relevant preclinical models. They would allow addressing specific questions such as the therapeutic efficacy of FR-targeting agents in tumor (mouse) models of multi-resistance and in mouse models of metastases formation.
叶酸受体（FR）在多种妇科癌症类型中均有表达。它已被广泛用于与诊断和治疗探针的叶酸缀合物进行肿瘤靶向。宫颈KB肿瘤细胞已发展成为基于叶酸的（放射性）缀合物临床前研究的标准模型。在本研究中，对一组表达FR的人类癌细胞系进行了体外研究，并研究了它们在小鼠体内作为异种移植物生长的能力，这些细胞系包括宫颈（HeLa、KB、KB-V1）、卵巢（IGROV-1、SKOV-3、SKOV-3.ip）、绒毛膜癌（JAR、BeWo）和子宫内膜（EFE-184）肿瘤细胞。比较了FR在体外和体内的表达水平，并通过测定对常用化疗药物的敏感性以及另外两种相关肿瘤标志物HER2和L1-CAM的表达来对细胞系进行表征。结果发现，除了KB细胞外，其多药耐药的KB-V1亚克隆以及卵巢癌细胞系IGROV-1和SKOV-3.ip，可作为潜在更相关的临床前模型。它们将有助于解决特定问题，例如FR靶向药物在多药耐药肿瘤（小鼠）模型和转移形成小鼠模型中的治疗效果。
