Establishment and characterization of patient-derived xenograft and its
cell line of primary leiomyosarcoma of bone
Received: 20 February 2018 /Accepted: 12 April 2018 /Published online: 29 May 2018 / Editor: Tetsuji Okamoto
The Society for In Vitro Biology 2018
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.
Keywords Primary leiomyosarcoma of bone
Primary culture cells
Primary leiomyosarcoma (LMS) is an aggressive sarcoma that
originates from the smooth muscle. Primary LMS of bone is
quite rare, and most cases have been presented as small case
series (Evans and Sanerkin 1965;Breweretal.2012;Berlin
et al. 1987; Myers et al. 1991; Antonescu et al. 1997;
Hannachi Sassi et al. 1999;Gotoetal.2002; Bouaziz et al.
2005; Atalar et al. 2008; Adelani et al. 2009; Rekhi et al.
2011), making it difficult to extrapolate the results to the entire
patient population. The median affected age of patients with
primary LMS is 46–47 yr, ranging between 9 and 88 yr
(Adelani et al. 2009;Breweretal.2012). The primary affected
sites are the distal femur and proximal tibia (Berlin et al. 1987;
Young et al. 1988; Antonescu et al. 1997; Vera-Badillo et al.
2013) and occasionally the craniofacial skeleton (Soderholm
et al. 1988;Carteretal.1999; Izumi et al. 1995; Ikram et al.
2003; Ursick and Linthicum 2011; Kim et al. 2013). The
prognosis of primary LMS of bone is related to the stage of
diagnosis: the 5-yr overall survival rate ranges from 0% in
patients with stage 3 to 100% in patients with stages 1 or 2a
(Brewer et al. 2012). Curative treatment involves surgical re-
section with wide margins, and the effectiveness of neoadju-
vant chemotherapy remains debatable (Antonescu et al. 1997;
Adelani et al. 2009). Thus, it has become necessary to develop
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11626-018-0258-2) contains supplementary
material, which is available to authorized users.
* Tadashi Kondo
Department of Innovative Seeds Evaluation, National Cancer Center
Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Central Animal Division, National Cancer Center Research Institute,
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Division of Rare Cancer Research, National Cancer Center Research
Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Department of Pathology and Clinical Laboratories, National Cancer
Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Division of Musculoskeletal Oncology, National Cancer Center
Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
In Vitro Cellular & Developmental Biology - Animal (2018) 54:458–467