Characterization of cancer stem-like cells in chordoma

Aydemir, Esra; Bayrak, Ömer Faruk; Şahın, Fikrettin; Atalay, Başar; Köse, Gamze Torun; Özen, Mustafa; Sevli, Serhat; Dalan, Altay Burak; Yalvaç, Mehmet Emir; Dogruluk, Turgut; Türe, Uğur

doi:10.3171/2011.12.jns11430

Cited by 54 publications

(47 citation statements)

References 54 publications

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“…Moreover, CD24 high /CD133 high cells showed high expression of CD15. These data confirm and extend previous findings that CD15 and CD133 were candidates for CSC markers in chordoma, using a U-CH1 cell line [31]. Our data suggest that, as the stem markers, CD24, CD133, CD15, and ALDH could identify a residential CSC subpopulation in chordoma.…”

Section: Discussionsupporting

confidence: 91%

“…Certain established tumor cell lines have been reported to harbor residential CSC populations. Previous studies have defined the CSC population in a single chordoma cell line, U-CH1, as expressing CD15 and CD133 [31]. We investigated the relative expression levels (mean fluorescence intensity; MFI) of CD24, CD133, CD15, and ALDH in the CD24 high /CD133 high group in 4 chordoma cell lines (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionsupporting

confidence: 91%

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

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“…Cancer-stem-like chordoma cells were observed to grow in non-adherent soft agar medium, which is related to the capability of self-renewal. Differentiating agents also slowed down the migration speed of the treated cells [9,5]. Furthermore, coupling the chemotherapeutic agents etoposide and cisplatin with the differentiation agent retinoic acid increased the inhibition of cell growth in U-CH1 cells, suggesting that the chemoresistance of chordomas may be a result of the presence of cancer stem cells [8].…”

Section: Cancer-stem-like Cells In Chordomasmentioning

confidence: 96%

The molecular aspects of chordoma

et al. 2015

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Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

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“…Taking a closer look on the differently expressed genes it is remarkable that many of the downregulated genes in clival cell lines can be assigned to developmental processes. As chordoma cell lines have shown to express typical stem cell markers 35 , a connection to developmental processes seems to make sense. Amongst the downregulated genes in clivus chordomas, there were genes of the HOX family.…”

Section: Discussionmentioning

confidence: 99%

HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas

Jäger

Barth

Brüderlein

et al. 2017

Sci Rep

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Chordomas are rare tumours of the bone arising along the spine from clivus to sacrum. We compared three chordoma cell lines of the clivus region including the newly established clivus chordoma cell line, U-CH14, with nine chordoma cell lines originating from sacral primaries by morphology, on genomic and expression levels and with patient samples from our chordoma tissue bank. Clinically, chordomas of the clivus were generally smaller in size at presentation and patients with sacral chordomas had more metastases and more often recurrent disease. All chordoma cell lines had a typical physaliphorous morphology and expressed brachyury, S100-protein and cytokeratin. By expression analyses we detected differentially expressed genes in the clivus derived cell lines as compared to the sacral cell lines. Among these were HOXA7, HOXA9, and HOXA10 known to be important for the development of the anterior-posterior body axis. These results were confirmed by qPCR. Immunohistologically, clivus chordomas had no or very low levels of HOXA10 protein while sacral chordomas showed a strong nuclear positivity in all samples analysed. This differential expression of HOX genes in chordomas of the clivus and sacrum suggests an oncofetal mechanism in gene regulation linked to the anatomic site.

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Characterization of cancer stem-like cells in chordoma

Abstract: Cancer stem-like cell detection might be an important step in determining the recurrent and metastatic characteristics of chordoma. This finding may lead to the development of new approaches toward treatments of chordomas.

Cited by 54 publications

References 54 publications

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

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

The molecular aspects of chordoma

HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas

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