3-Dimensional micropillar drug screening identifies FGFR2-IIIC overexpression as a potential target in metastatic giant cell tumor
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Seung Tae Kim1,*, Jusun Kim1,*, Sumin Shin2,*, Sun Young Kim1, Dongwoo Lee3, Bosung Ku3, Yong Sung Shin4, Jhingook Kim2, Jeeyun Lee1
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Medical and Bio Device Inc. Suwon, Gyeonggi-Do, Korea
4Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea
*These authors contributed equally to this work
Jeeyun Lee, email: [email protected]
Jhingook Kim, email: [email protected]
Keywords: patient-derived cell (PDC), high-throughput screening (HTS), 3D culture
Received: January 10, 2017 Accepted: March 24, 2017 Published: April 06, 2017
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.
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