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Characteristics of human Ewing/PNET sarcoma models.

Teicher BA, Bagley RG, Rouleau C, Kruger A, Ren Y, Kurtzberg L - Ann Saudi Med (2011 Mar-Apr)

Bottom Line: Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma.Many Ewing sarcoma clinical specimens express the cell surface protein endosialin.With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets.

View Article: PubMed Central - PubMed

Affiliation: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA. beverlyteicher@aol.com

ABSTRACT
Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

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Representative complex karyotype of the A673 cell line showing multiple rearrangements, including a chromosome 11 and 22 fusion, b: Fluorescence in situ hybridization (FISH) analysis for EWSR1 in A673 Ewing sarcoma cells.19
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Figure 1: Representative complex karyotype of the A673 cell line showing multiple rearrangements, including a chromosome 11 and 22 fusion, b: Fluorescence in situ hybridization (FISH) analysis for EWSR1 in A673 Ewing sarcoma cells.19

Mentions: Seventeen human Ewing/PNET sarcoma cell lines that are currently in use to study these diseases are listed in Table 1. Some of the lines were established in the 1970s; and others, more recently. There is variable information on the origin of the lines as well as varied levels of molecular characterization. For example, the SK-NEP-1 line established in 1971 was originally designated as Wilms tumor; however, through molecular profiling it was recently shown to express the EWS/FLI1 gene fusion transcript and thus is now known to be a Ewing sarcoma.15 Similarly, the Rh1 xenograft which was derived from a patient whose diagnosis was rhabdomyosarcoma, also expresses an Ewing sarcoma gene expression profile and has confirmed expression of the EWS/FLI1 fusion transcript; thus it is an Ewing sarcoma and was renamed EW8(Rh1). Several other lines designated as Ewing sarcoma were confirmed expressers of the EWS/FLI1 fusion transcript. The cell line CHLA-9 was established at diagnosis from a 14-year-old female with a thoracic PNET, and the CHLA-10 line was established from the same patient after 4 cycles of chemotherapy, at which time the tumor cells had become p53 mutant.16 The A673 cell line was described in 1973 as being from a patient with a possible rhabdomyosarcoma; however, recent cytogenetic testing and molecular profiling established that A673 cells express the EWS/FLI1 transcription factor and confirmed that A673 cells are Ewing sarcoma (Figure 1).17–19 A673 cells grown as a human tumor xenograft in immunodeficient mice have proven to be a useful in vivo model to explore the biology of tumor growth and to identify therapeutic targets for sarcomas.


Characteristics of human Ewing/PNET sarcoma models.

Teicher BA, Bagley RG, Rouleau C, Kruger A, Ren Y, Kurtzberg L - Ann Saudi Med (2011 Mar-Apr)

Representative complex karyotype of the A673 cell line showing multiple rearrangements, including a chromosome 11 and 22 fusion, b: Fluorescence in situ hybridization (FISH) analysis for EWSR1 in A673 Ewing sarcoma cells.19
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102479&req=5

Figure 1: Representative complex karyotype of the A673 cell line showing multiple rearrangements, including a chromosome 11 and 22 fusion, b: Fluorescence in situ hybridization (FISH) analysis for EWSR1 in A673 Ewing sarcoma cells.19
Mentions: Seventeen human Ewing/PNET sarcoma cell lines that are currently in use to study these diseases are listed in Table 1. Some of the lines were established in the 1970s; and others, more recently. There is variable information on the origin of the lines as well as varied levels of molecular characterization. For example, the SK-NEP-1 line established in 1971 was originally designated as Wilms tumor; however, through molecular profiling it was recently shown to express the EWS/FLI1 gene fusion transcript and thus is now known to be a Ewing sarcoma.15 Similarly, the Rh1 xenograft which was derived from a patient whose diagnosis was rhabdomyosarcoma, also expresses an Ewing sarcoma gene expression profile and has confirmed expression of the EWS/FLI1 fusion transcript; thus it is an Ewing sarcoma and was renamed EW8(Rh1). Several other lines designated as Ewing sarcoma were confirmed expressers of the EWS/FLI1 fusion transcript. The cell line CHLA-9 was established at diagnosis from a 14-year-old female with a thoracic PNET, and the CHLA-10 line was established from the same patient after 4 cycles of chemotherapy, at which time the tumor cells had become p53 mutant.16 The A673 cell line was described in 1973 as being from a patient with a possible rhabdomyosarcoma; however, recent cytogenetic testing and molecular profiling established that A673 cells express the EWS/FLI1 transcription factor and confirmed that A673 cells are Ewing sarcoma (Figure 1).17–19 A673 cells grown as a human tumor xenograft in immunodeficient mice have proven to be a useful in vivo model to explore the biology of tumor growth and to identify therapeutic targets for sarcomas.

Bottom Line: Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma.Many Ewing sarcoma clinical specimens express the cell surface protein endosialin.With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets.

View Article: PubMed Central - PubMed

Affiliation: Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA. beverlyteicher@aol.com

ABSTRACT
Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.

Show MeSH
Related in: MedlinePlus