Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone

Rieko Oyama, Mami Takahashi, Fusako Kito, Marimu Sakumoto, Kumiko Shiozawa, Zhiwei Qiao, Akihiko Yoshida, Makoto Endo, Akira Kawai, Tadashi Kondo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Primary leiomyosarcoma (LMS) of bone is a rare and aggressive mesenchymal malignancy that differentiates toward smooth muscle. Complete resection is the only curable treatment, and novel therapeutic approaches for primary LMS of bone have long been desired. Patient-derived xenografts (PDXs) and cell lines are invaluable tools for preclinical studies. Here, we established PDXs from a patient with primary LMS of bone and a cell line from an established PDX. Bone primary LMS tissue was subcutaneously implanted into highly immune-deficient mice. After two passages, a piece of the tumor was subjected to tissue culturing, and a morphological evaluation and proteomic analysis were performed on the PDX and the established cell line. Moreover, the responses of the established cell line to anti-cancer drugs were examined. Microscopic observations revealed that the PDX tumors retained their original histology. The cell line was established from the third-generation PDX and named NCC-LMS1-X3-C1. The cells were maintained for over 18 mo and 40 passages. The cells exhibited a spindle shape and aggressive growth. Mass spectrometric protein identification revealed that the original tumor tissue, PDX tumor tissue, and NCC-LMS1-X3-C1 cells had similar but distinct protein expression profiles. We previously established the cell line, NCC-LMS1-C1, from the tumor tissue of same patient. We found that the response to drug treatments was different between NCC-LMS1-X3-C1 and NCC-LMS1-C1, suggesting the heterogeneous traits of tumor cells in the identical tumor tissue. This set of PDXs and stable cell line will be a useful resource for bone LMS research.

Original languageEnglish
Pages (from-to)458-467
Number of pages10
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 1 2018
Externally publishedYes

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Leiomyosarcoma
Heterografts
Bone and Bones
Cell Line
Neoplasms
Pharmaceutical Preparations
Proteomics
Smooth Muscle
Histology
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

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Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone. / Oyama, Rieko; Takahashi, Mami; Kito, Fusako; Sakumoto, Marimu; Shiozawa, Kumiko; Qiao, Zhiwei; Yoshida, Akihiko; Endo, Makoto; Kawai, Akira; Kondo, Tadashi.

In: In Vitro Cellular and Developmental Biology - Animal, Vol. 54, No. 6, 01.06.2018, p. 458-467.

Research output: Contribution to journalArticle

Oyama, Rieko ; Takahashi, Mami ; Kito, Fusako ; Sakumoto, Marimu ; Shiozawa, Kumiko ; Qiao, Zhiwei ; Yoshida, Akihiko ; Endo, Makoto ; Kawai, Akira ; Kondo, Tadashi. / Establishment and characterization of patient-derived xenograft and its cell line of primary leiomyosarcoma of bone. In: In Vitro Cellular and Developmental Biology - Animal. 2018 ; Vol. 54, No. 6. pp. 458-467.
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AU - Kito, Fusako

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AU - Shiozawa, Kumiko

AU - Qiao, Zhiwei

AU - Yoshida, Akihiko

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AU - Kondo, Tadashi

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AB - Primary leiomyosarcoma (LMS) of bone is a rare and aggressive mesenchymal malignancy that differentiates toward smooth muscle. Complete resection is the only curable treatment, and novel therapeutic approaches for primary LMS of bone have long been desired. Patient-derived xenografts (PDXs) and cell lines are invaluable tools for preclinical studies. Here, we established PDXs from a patient with primary LMS of bone and a cell line from an established PDX. Bone primary LMS tissue was subcutaneously implanted into highly immune-deficient mice. After two passages, a piece of the tumor was subjected to tissue culturing, and a morphological evaluation and proteomic analysis were performed on the PDX and the established cell line. Moreover, the responses of the established cell line to anti-cancer drugs were examined. Microscopic observations revealed that the PDX tumors retained their original histology. The cell line was established from the third-generation PDX and named NCC-LMS1-X3-C1. The cells were maintained for over 18 mo and 40 passages. The cells exhibited a spindle shape and aggressive growth. Mass spectrometric protein identification revealed that the original tumor tissue, PDX tumor tissue, and NCC-LMS1-X3-C1 cells had similar but distinct protein expression profiles. We previously established the cell line, NCC-LMS1-C1, from the tumor tissue of same patient. We found that the response to drug treatments was different between NCC-LMS1-X3-C1 and NCC-LMS1-C1, suggesting the heterogeneous traits of tumor cells in the identical tumor tissue. This set of PDXs and stable cell line will be a useful resource for bone LMS research.

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