Establishment and detailed functional and molecular genetic characterisation of a novel sacral chordoma cell line, MUG-Chor1

Rinner, Beate; Froehlich, Elke Verena; Buerger, Karin; Knausz, Heike; Lohberger, Birgit; Scheipl, Susanne; Fischer, Carina; Leithner, Andreas; Godballe, Christian; Trajanoski, Slave; Szuhai, Károly; Liegl, Bernadette

doi:10.3892/ijo.2011.1235

Cited by 47 publications

(58 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the potential of anti-PD-L1 antibody therapy in chordoma has not previously been shown. We first examined whether IFN-γ could modulate expression of MHC-I and PD-L1 in chordoma cell lines established from 4 chordoma patients [18-21]. All 4 cell lines expressed HLA-ABC and PD-L1, and both molecules were upregulated by IFN-γ in all 4 cell lines (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab

et al. 2016

View full text Add to dashboard Cite

Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8+ T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.

show abstract

Section: Resultsmentioning

confidence: 99%

Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Early detection is a key to better management of the disease and increasing number of molecular studies are being undertaken using chordoma tissues and the few chordoma cell lines that have been developed and are available to the scientific community. 9,10 Patient-derived chordoma xenografts have also been recently developed for preclinical assessment of novel therapies and drug testing.…”

Section: Discussionmentioning

confidence: 99%

“…Two chordoma cell lines (UCH-1 and MUG-Chor1) 9,10 were kindly provided by the Chordoma Foundation. UCH-1 was maintained in IMDM (Invitrogen 12400)/RPMI 1,640 (Sigma R8758) medium (4 IMDM: 1 RPMI) with 10% FBS and 1% PenStrep at 37 C, 5% CO 2 .…”

Section: Chordoma Cell Linesmentioning

confidence: 99%

Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas

et al. 2015

View full text Add to dashboard Cite

Chordomas are an aggressive rare type of malignant bone tumors arising from the remnant of the notochord. Chordomas occur mainly in vertebral bones and account for 1-4% of malignant bone tumors. Management and treatment of chordomas are difficult as they are resistant to conventional chemotherapy; therefore, they are mainly treated with surgery and radiation therapy. In this study, we performed DNA methylation profiling of 26 chordomas and normal nucleus pulposus samples plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450 BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was used to confirm the methylation data. Gene expression was analyzed using RT-PCR before and after 5-aza-2'-deoxycytidine (5-azaDC) treatment of chordoma cell lines. Analysis of the HumanMethylation450 BeadChip data led to the identification of 8,819 loci (2.9%) that were significantly differentially methylated (>0.2 average b-value difference) between chordomas and nucleus pulposus samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were hypomethylated, compared to 2,951 (33.5%) loci that were hypermethylated in chordomas compared to controls. From the 2,951 differentially hypermethylated probes, 33.3% were localized in the promoter region (982 probes) and, among these, 104 probes showed cancer-specific hypermethylation. Ingenuity Pathway Analysis indicates that the cancer-specific differentially methylated loci are involved in various networks including cancer disease, nervous system development and function, cell death and survival, cellular growth, cellular development, and proliferation. Furthermore, we identified a subset of probes that were differentially methylated between recurrent and non-recurrent chordomas. BeadChip methylation data was confirmed for these genes and gene expression was shown to be upregulated in methylated chordoma cell lines after treatment with 5-azaDC. Understanding epigenetic changes in chordomas may provide insights into chordoma tumorigenesis and development of epigenetic biomarkers.

show abstract

“…It can be debated whether these cells are still to be considered true chordoma cells. Chordoma cells tend not to thrive in vitro and proliferate slowly as evidenced by the limited number of commercially available cell lines (19,20). The CH1 and CH2 cells are no different in that respect.…”

Section: Discussion / Conclusionmentioning

confidence: 99%