New established cell lines from undifferentiated pleomorphic sarcoma for in vivo study

Abstract

As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS.

Novel PD-L1- and collagen-expressing patient-derived cell line of undifferentiated pleomorphic sarcoma (JBT19) as a model for cancer immunotherapy

“…Cell lines are widely used for in vitro and in vivo models to investigate the biological behavior of tumor cells and to investigate the mechanisms of their resistance to therapy. Many of UPS cell lines were established in multiple studies in previous years 49 – 52 . However, although the establishment of new UPS cell lines is ongoing 52 , there are still not only a limited number of UPS cell lines available through public depositories 17 , but, to our knowledge, none of the studies previously published directly addressed and investigated their suitability for immunotherapeutic research.…”

“…Many of UPS cell lines were established in multiple studies in previous years 49 – 52 . However, although the establishment of new UPS cell lines is ongoing 52 , there are still not only a limited number of UPS cell lines available through public depositories 17 , but, to our knowledge, none of the studies previously published directly addressed and investigated their suitability for immunotherapeutic research. The newly described JBT19 cell line in this study was not only largely described on the molecular level and found suitable for both in vitro and in vivo studies but also shown to be suitable for immunotherapeutic research.…”

THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059

“…The human colon carcinoma cell line, HCT116, and human non-small cell lung cancer cell lines, A549 and H460, were obtained from the American Type Culture Collection (Manassa, VA, USA). KNCC-STS2 cell line was newly established at National Cancer Center, South Korea [ 29 ]. All cells were authenticated by short-tandem repeat (STR) polymerase chain reaction (PCR) method in 2022 and 2023 by NCC genomic core facility.…”

“…Equal amounts of proteins were mixed with 2 × sample buffer and heated at 95 °C for 7 min and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 8–10% acrylamide gels followed by transfer to polyvinylidene difluoride membranes. Immunoblotting was performed as described previously [ 29 ].…”

Experimental models of tumor growth in soft tissue sarcomas

“…Another study showed that models of undifferentiated pleomorphic sarcoma obtained in immunodeficient mice from primary lines were similar in histological characteristics and protein expression of Ki-67 and CD31 to patients' tumor tissues [36]. However, the clonal composition of tumors in vivo and patients, as well as their transcriptomic features were different, which caused differences in the effectiveness of doxorubicin, gemcitabine and cisplatin [36].…”