Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors
Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-02-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-1128-z |
| _version_ | 1811323357637902336 |
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| author | Rieko Oyama Fusako Kito Mami Takahashi Emi Hattori Rei Noguchi Yoko Takai Marimu Sakumoto Zhiwei Qiao Shunichi Toki Masato Sugawara Yoshikazu Tanzawa Eisuke Kobayashi Fumihiko Nakatani Shintaro Iwata Akihiko Yoshida Akira Kawai Tadashi Kondo |
| author_facet | Rieko Oyama Fusako Kito Mami Takahashi Emi Hattori Rei Noguchi Yoko Takai Marimu Sakumoto Zhiwei Qiao Shunichi Toki Masato Sugawara Yoshikazu Tanzawa Eisuke Kobayashi Fumihiko Nakatani Shintaro Iwata Akihiko Yoshida Akira Kawai Tadashi Kondo |
| author_sort | Rieko Oyama |
| collection | DOAJ |
| description | Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients. Methods We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines. Results We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents. Conclusion The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs. |
| first_indexed | 2024-04-13T13:52:36Z |
| format | Article |
| id | doaj.art-d1f5d633b68e4e27ad67c4a56f2c9c08 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-13T13:52:36Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-d1f5d633b68e4e27ad67c4a56f2c9c082022-12-22T02:44:17ZengBMCCancer Cell International1475-28672020-02-0120111510.1186/s12935-020-1128-zEstablishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumorsRieko Oyama0Fusako Kito1Mami Takahashi2Emi Hattori3Rei Noguchi4Yoko Takai5Marimu Sakumoto6Zhiwei Qiao7Shunichi Toki8Masato Sugawara9Yoshikazu Tanzawa10Eisuke Kobayashi11Fumihiko Nakatani12Shintaro Iwata13Akihiko Yoshida14Akira Kawai15Tadashi Kondo16Department of Innovative Seeds Evaluation, National Cancer Center Research InstituteDepartment of Innovative Seeds Evaluation, National Cancer Center Research InstituteCentral Animal Division, National Cancer Center Research InstituteDivision of Rare Cancer Research, National Cancer Center Research InstituteDivision of Rare Cancer Research, National Cancer Center Research InstituteDepartment of Innovative Seeds Evaluation, National Cancer Center Research InstituteDepartment of Innovative Seeds Evaluation, National Cancer Center Research InstituteDivision of Rare Cancer Research, National Cancer Center Research InstituteDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDepartment of Pathology and Clinical Laboratories, National Cancer Center HospitalDivision of Musculoskeletal Oncology, National Cancer Center HospitalDepartment of Innovative Seeds Evaluation, National Cancer Center Research InstituteAbstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients. Methods We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines. Results We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents. Conclusion The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.http://link.springer.com/article/10.1186/s12935-020-1128-zMalignant peripheral nerve sheath tumorXenograftPrimary cultureDrug screening |
| spellingShingle | Rieko Oyama Fusako Kito Mami Takahashi Emi Hattori Rei Noguchi Yoko Takai Marimu Sakumoto Zhiwei Qiao Shunichi Toki Masato Sugawara Yoshikazu Tanzawa Eisuke Kobayashi Fumihiko Nakatani Shintaro Iwata Akihiko Yoshida Akira Kawai Tadashi Kondo Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors Cancer Cell International Malignant peripheral nerve sheath tumor Xenograft Primary culture Drug screening |
| title | Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors |
| title_full | Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors |
| title_fullStr | Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors |
| title_full_unstemmed | Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors |
| title_short | Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors |
| title_sort | establishment and characterization of patient derived cancer models of malignant peripheral nerve sheath tumors |
| topic | Malignant peripheral nerve sheath tumor Xenograft Primary culture Drug screening |
| url | http://link.springer.com/article/10.1186/s12935-020-1128-z |
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