Abstract
We established two patient derived tumor cells (PDCs) from right and left pulmonary metastatic lesions respectively of a patient with giant cell tumor. At that time, patient-derived tumor cells from right and left surgical specimens were collected and cultured. High-throughput screening (HTS) for 24 drugs was conducted with a micropillar/microwell chip platform using giant cell tumor PDCs. Using 6 doses per drug in 6 replicates for giant cell tumor PDCs, the dose response curves and corresponding IC50 values were calculated from the scanned images using the S+ Chip Analyzer. A sensitive response was more significantly achieved for AZD4547 (FGFR2 inhibitor) in giant cell tumor PDCs originated from the right pulmonary nodule under the micropillar/microwell chip platform using 3D culture. This sensitivity was consistent with the target expression patterns of giant cell tumor PDCs (FGFR2-IIIC mRNA expression in giant cell tumor PDCs originated from the right pulmonary nodule was increased significantly as compared to those originated from left). However, in a conventional 2D cultured MTT assay, there was no difference for IC50 values of AZD4547 between giant cell tumor PDCs originated from right and left pulmonary nodules. An HTS platform based on 3D culture on micropillar/microwell chips and PDC models could be applied as a useful preclinical tool to evaluate the intrapatient tumor/response heterogeneity. This platform based on 3D culture might reflect far better the relation between the tumor-biology and the matched targeted agent as compared to a conventional 2D cultured MTT assay.
Highlights
Giant cell tumor of bone (GCT) is an aggressive osteolytic and potentially metastatic bone tumor, which has a predilection anatomic sites of long bones such as distal femur, proximal tibia and distal radius [1]
A sensitive response was more significantly achieved for AZD4547 (FGFR2 inhibitor) in giant cell tumor patient derived tumor cells (PDCs) originated from the right pulmonary nodule under the micropillar/microwell chip platform using 3D culture
This sensitivity was consistent with the target expression patterns of giant cell tumor PDCs (FGFR2-IIIC mRNA expression in giant cell tumor PDCs originated from the right pulmonary nodule was increased significantly as compared to those originated from left)
Summary
Giant cell tumor of bone (GCT) is an aggressive osteolytic and potentially metastatic bone tumor, which has a predilection anatomic sites of long bones such as distal femur, proximal tibia and distal radius [1]. Distant metastasis of GCTs of the bone is extremely rare. Lung metastasis of a benign GCT of the bone was first reported in 1926. One of the most common organs for distant metastasis from GCT is lung, ranging from 1 to 9% in incidence [6,7,8,9]. Fibroblast growth factor receptor (FGFR) is a transmembrane tyrosine kinase receptor that mediates angiogenesis, as well as proliferation and survival of cancer cells [10, 11]. In GCT, FGF-2 stimulates FGFR2 expression, resulting in increased alkaline phosphatase (ALP) and osteopontin expression. Inhibition of FGFR2 through siRNA decreased the expression of osteopontin in GCT stromal cells resulting in FGF2 ligand induced downstream signaling pathway, and possibly cell growth inhibition [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
