Abstract
The folate receptor alpha (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.
Highlights
The folate receptor alpha (FR) has emerged as an interesting tumor target due to its overexpression in a variety of tumor types, including several gynecological cancers of epithelial origin [1,2,3]
We investigated tumor cells of cervical, ovarian and endometrial origin as well as choriocarcinoma cells
KB, KB-V1, IGROV-1 and SKOV-3.ip cells revealed to be appropriate for in vitro experiments and could be efficiently grown in mice allowing tumor targeting in vivo
Summary
The folate receptor alpha (FR) has emerged as an interesting tumor target due to its overexpression in a variety of tumor types, including several gynecological cancers of epithelial origin [1,2,3]. Due to favorable FR-targeting properties, the vitamin folic acid has been investigated extensively as a ligand to deliver attached diagnostic and therapeutic payloads for imaging and therapy of FR-expressing cancer [6]. This targeting concept is based on the accessibility of folic acid for chemical derivatization allowing the conjugation of even bulky entities without losing FR-binding affinity [7]. Folate conjugates of fluorescent probes have been developed for intraoperative imaging of ovarian tumors allowing more radical cytoreductive surgery in patients [11]. A number of otherwise highly toxic agents have been used in conjunction with folic acid to allow specific accumulation in FR-expressing tumor cells for cancer therapy in clinical trials [19,20,21,22,23,24]
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