Establishment and characterization of a novel chordoma cell line: CH22

Liu, Xianzhe; Nielsen, G. Petur; Rosenberg, Andrew E.; Waterman, Peter; Yang, Wei-Zhong; Choy, Edwin; Sassi, Slim; Yang, Shuai; Harmon, David C.; Yang, Cao; Schwab, Joseph H.; Kobayashi, Eisuke; Mankin, Henry J.; Xavier, Ramnik J.; Weissleder, Ralph; Duan, Zhenfeng; Hornicek, Francis J.

doi:10.1002/jor.22113

Cited by 37 publications

(31 citation statements)

References 22 publications

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“…Our report of this behavior is both novel and significant, as prior studies of brachyury positivity and copy number aberrations in cultured U-CH2b cells 2 were not predictive of the potential to generate tumor xenografts in vivo, pointing to the need for additional molecular markers to understand tumor progression. Several prior studies have confirmed that morphological appearance, cytoskeletal protein staining (vimentin, cytokeratins), and positivity for S100 and brachyury are essential for characterizing a chordoma xenograft; 11,12,14,20 however, our results suggest that other molecular markers may be needed to distinguish tumorigenic potential and growth kinetics.…”

Section: Discussionsupporting

confidence: 61%

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Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines

Karikari¹,

Gilchrist

Jing

et al. 2014

SPI

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Object Chordoma cells can generate solid-like tumors in xenograft models that express some molecular characteristics of the parent tumor, including positivity for brachyury and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma tumor growth, as well as the cell lines needed to advance treatment. The objective in this study was to isolate a novel primary chordoma cell source and analyze the characteristics of tumor growth in a mouse xenograft model for comparison with the established U-CH1 and U-CH2b cell lines. Methods Primary cells from a sacral chordoma, called “DVC-4,” were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages and characterized for expression of CD24 and brachyury. While brachyury is believed essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγnull mice. The percentage of solid tumors formed, time to maximum tumor size, and immunostaining scores for CD24 and brachyury (intensity scores of 0–3, heterogeneity scores of 0–1) were reported and evaluated to test differences across groups. Results The DVC-4 cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible tumors in less than 50% of injected sites. Brachyury staining was similar among tumors derived from all 3 cell types and was intensely positive (scores of 2–3) in a majority of tissue sections. In contrast, differences in the pattern and intensity of staining for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of intense and uniform staining in a majority of U-CH1 tumor sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2–3). In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1–2) with a predominantly heterogeneous staining pattern. Conclusions This is the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity was discovered despite evidence of chordoma-like characteristics in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining for CD24 was observed, which may correspond to their similar potential to grow tumors. In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize that many markers, including CD24, may be useful in distinguishing among chordoma cell types and their tumorigenicity in vivo.

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Section: Discussionsupporting

confidence: 61%

“…11,12,14,20 To date, very few chordoma cell lines have been reported, namely U-CH1 17 and U-CH2b, 2 along with many more putative chordoma cell lines. Only a few of these have been shown to generate tumors in established mouse xenograft models and to retain molecular characteristics of the parent tumor and expanded cells.…”

mentioning

confidence: 99%

Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines

Karikari¹,

Gilchrist

Jing

et al. 2014

SPI

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“…CH22, another human chordoma cell line, was established in our laboratory as previously reported (23). All cell lines used in this study have been tested and shown to be free of mycoplasma and bacterial.…”

Section: Methodsmentioning

confidence: 99%

Expression and Therapeutic Potential of SOX9 in Chordoma

Chen

Garbutt

Spentzos

et al. 2017

Clinical Cancer Research

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Purpose Conventional chemotherapeutic agents are ineffective in the treatment of chordoma. We investigated the functional roles and therapeutic relevance of the sex-determining region Y (SRY)-box 9 (SOX9) in chordoma. Experimental Design SOX9 expression was examined by immunohistochemistry (IHC) using 50 chordoma tissue samples. SOX9 expression in chordoma cell lines was examined by Western blot and immunofluorescence assays. We used synthetic human SOX9 siRNA to inhibit the expression of SOX9. Cell proliferation ability and cytotoxicity of inhibiting SOX9 were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and clonogenic assays. The effect of SOX9 knockdown on chordoma cell motility was evaluated by a wound healing assay and a transwell invasion chamber assay. Knockdown of SOX9 induced apoptosis, cell cycle arrest as well as decreased expression of cancer stem cell markers were determined by Western blot and flow cytometric assays. The effect of the combination of SOX9 siRNA and the chemotherapeutic drug doxorubicin/cisplatin on chordoma cells was assessed by a MTT assay. Results Tissue microarray (TMA) and IHC analysis showed that SOX9 is broadly expressed in chordomas and that higher expression levels of SOX9 correlated with a poor prognosis. RNA interference (RNAi)-mediated knockdown of SOX9 inhibited chordoma cell growth, decreased cell motility, and induced apoptosis as well as cell cycle arrest. Moreover, the combination of SOX9 inhibition and chemotherapeutic drugs had an enhanced anti-cancer effect on chordoma cells. Conclusions Our results demonstrate that SOX9 plays a crucial role in chordoma. Targeting SOX9 provides a new rationale for treatment of chordoma.

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“…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%