Engagement of CD99 Induces Apoptosis Through a Calcineurin-Independent Pathway in Ewing's Sarcoma Cells

Sohn, Hyung Sun; Choi, Eun Young; Kim, Soon Ha; Lee, Im Soon; Chung, Doo Hyun; Sung, U.; Hwang, Duck Ho; Cho, Sa Sun; Jun, Byung Hoon; Jang, Ja June; G., Je; Park, Seong Hoe

doi:10.1016/s0002-9440(10)65707-0

Cited by 87 publications

(72 citation statements)

References 27 publications

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“…In the present case, the primary tumor did not express keratin but the xenograft was reactive with keratin. This result supports that Ewing's sarcoma may represent the stage of either very early pluripotential cells or primitive neuroectodermal cells that can differentiate along a neuronal, glial, Schwannian, melanocytic, neuroendocrine, or even ectomesenchymal pathway (Sohn et al 1998).…”

supporting

confidence: 79%

Establishment and Characterization of a Clonal Human Extraskeletal Ewing's Sarcoma Cell Line, EES1

Hatori

Doi

Watanabe

et al. 2006

Tohoku J. Exp. Med.

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Ewing's sarcoma, a small round cell sarcoma arising in soft tissue as well as the bone, is one of the most malignant tumors in children and young adults. Few established cell lines of extraskeletal Ewing's sarcoma (EES) have been reported, which made it difficult to examine the biological features of EES. Therefore, we have established a new clonal cell line of EES. We report its morphological characters, results of chromosomal and immunohistochemical analysis. A piece of tumor obtained from the 18-year-old female patient with EES was xenografted in a nude mouse. In vitro subcultured cells were then obtained from this xenograft. A clonal cell line was subsequently established by limiting dilution and designated EES1. EES1 cells had a doubling time of 24 hours. In the xenografted tumor, the cells expressed vimentin, CD99 (MIC2), neuron specific enolase (NSE) and cytokeratin. The original tumor cells also expressed vimentin, CD 99, and NSE, but was negative for cytokeratin. The morphological and immunohistochemical features of this cell line established, except for cytokeratin expression, were consistent with those of the primary tumor. Cytogenetic analysis of EES1 revealed chromosomal translocation of t(11; 12)(q24;ql2). The chimeric fusion of the Ewing's sarcoma gene in band 22q12 with the Friend leukemia virus integration-1 gene in band 11q24 was also demonstrated. Fluorescence in situ hybridization further confirmed the presence of translocation involving the Ewing's sarcoma gene in both the primary tumor and EES1 cells. In conclusion, we have established a human EES cell line EES1, which will provide a useful model for studying various aspects of human EES.

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supporting

confidence: 79%

Establishment and Characterization of a Clonal Human Extraskeletal Ewing's Sarcoma Cell Line, EES1

Hatori

Doi

Watanabe

et al. 2006

Tohoku J. Exp. Med.

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“…Recent reports demonstrate that, in the absence of caspase activity, other apoptotic events, such as phosphatidylserine (PS) externalisation to the cell surface, mitochondrial alterations, membrane blebbing, cell shrinkage and nuclear condensation/fragmentation can still occur. [148][149][150][151][152][153] The activity of the caspases can be inhibited by the synthetic peptide Ac-DEVD-CHO, which mimics the recognition site in PARP, a caspase-3 substrate. 154 Interestingly, the hsp70 molecule has a conserved C-terminal sequence -EEVD.…”

Section: Figurementioning

confidence: 99%

Heat shock proteins – modulators of apoptosis in tumour cells

2000

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Apoptosis is a genetically programmed, physiological method of cell destruction. A variety of genes are now recognised as positive or negative regulators of this process. Expression of inducible heat shock proteins (hsp) is known to correlate with increased resistance to apoptosis induced by a range of diverse cytotoxic agents and has been implicated in chemotherapeutic resistance of tumours and carcinogenesis. Intensive research on apoptosis over the past number of years has provided significant insights into the mechanisms and molecular events that occur during this process. The modulatory effects of hsps on apoptosis are well documented, however, the mechanisms of hsp-mediated protection against apoptosis remain to be fully defined, although several hypotheses have been proposed. Elucidation of these mechanisms should reveal novel targets for manipulating the sensitivity of leukaemic cells to therapy. This review aims to explain the currently understood process of apoptosis and the effects of hsps on this process. Several proposed mechanisms for hsp protection against apoptosis and the therapeutic implications of hsps in leukaemia are also discussed. Leukemia (2000) 14, 1161-1173.

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“…In pathological conditions, the triggering of CD99 results in the induction of cell-cell adhesion and apoptosis of Ewing's sarcoma cells (Sohn et al, 1998;Scotlandi et al, 2000;Cerisano et al, 2004). Moreover, it has recently been found that CD99 downregulation is essential in osteosarcoma to express full malignancy (Manara et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

CD99 isoforms dictate opposite functions in tumour malignancy and metastases by activating or repressing c-Src kinase activity

et al. 2007

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CD99 gene encodes two distinct proteins, produced by alternative splicing of CD99 gene transcript. Full-length CD99 isoform (CD99wt) is formed by an extracellular domain, followed by a transmembrane domain and a 36 amino-acid intracytoplasmic domain, which is partially deleted in the truncated, short form (CD99sh). A differential expression of these two CD99 molecules can lead to distinct functional outcomes in lymphocytes. To investigate the functional effects of CD99 molecules on malignancy, forced overexpression of the two CD99 isoforms was induced in osteosarcoma and prostate cancer cells. The two isoforms exhibited opposite functions: the major form dramatically inhibits anchorage-independent growth, anoikis resistance, migration and metastasis, whereas the CD99sh remarkably favours the phenomena. A mechanistic analysis of CD99-transfected osteosarcoma cells points to involvement of c-Src family kinase activity in regulating CD99 functions in malignancy. Ser168 residue of CD99 plays a pivotal role in the reversion of the malignant phenotype. Our findings highlight the involvement of CD99 in crucial processes of cancer malignancy, serving as a curtain raiser for this, so far neglected molecule. In addition, a dualistic role for the two CD99 isoforms was shown in agreement with what was observed for other cell adhesion molecules.

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Engagement of CD99 Induces Apoptosis Through a Calcineurin-Independent Pathway in Ewing's Sarcoma Cells

Cited by 87 publications

References 27 publications

Establishment and Characterization of a Clonal Human Extraskeletal Ewing's Sarcoma Cell Line, EES1

Establishment and Characterization of a Clonal Human Extraskeletal Ewing's Sarcoma Cell Line, EES1

Heat shock proteins – modulators of apoptosis in tumour cells

CD99 isoforms dictate opposite functions in tumour malignancy and metastases by activating or repressing c-Src kinase activity

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