Credentialing Preclinical Pediatric Xenograft Models Using Gene Expression and Tissue Microarray Analysis

Whiteford, Craig C.; Bilke, Sven; Greer, Braden T.; Chen, Qingrong; Braunschweig, Till; Cenacchi, Nicola; Wei, Jun S.; Smith, Malcolm A.; Houghton, Peter J.; Morton, Christopher L.; Reynolds, C. Patrick; Lock, Richard B.; Görlick, Richard; Khanna, Chand; Thiele, Carol J.; Takikita, Mikiko; Catchpoole, Daniel; Hewitt, Stephen M.; Khan, Javed

doi:10.1158/0008-5472.can-06-0610

Cited by 104 publications

(92 citation statements)

References 24 publications

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“…When a model anti-endosialin-toxin conjugate was tested in the endosialin-positive SK-N-AS cell line and in the endosialin-negative HT-1080 fibrosarcoma cell line, the results showed that antigen-specific growth inhibition could be achieved in vitro via internalization of anti-endosialin (11). All 10 human neuroblastoma cell lines studied, both MYCN-amplified and non-MYCN-amplified, have been independently confirmed to be neuroblastoma cell lines using multiple mRNA and protein markers and clustering analysis (24). The presence of endosialin in MYCN-amplified lines is in accordance with the reported advanced clinical stage of some of the neuroblastoma lines.…”

Section: Discussionsupporting

confidence: 63%

Endosialin: A novel malignant cell therapeutic target for neuroblastoma

Rouleau¹,

Smale²,

Sancho³

et al. 2011

Int J Oncol

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Abstract. Endosialin emerged recently as a potential therapeutic target for sarcoma. Since some sarcoma subtypes, such as Ewing's sarcoma, show characteristics of neuroendocrine differentiation, we wondered whether cancers with neuroendocrine properties and/or neuroectodermal origin, such as neuroblastoma, small cell lung cancer and melanoma, may express endosialin. Endosialin protein expression was surveyed in neuroblastoma, small cell lung cancer and melanoma in human clinical specimens by immunohistochemistry (IHC) and in human cell lines by flow cytometry. Side population cells were examined to determine whether cancer stem cells can express endosialin. Endosialin-expressing neuroblastoma cell lines were implanted in immunodeficient mice and allowed to grow. The xenograft tumors were resected and tested for endosialin expression by IHC. In human clinical specimens, vascular endosialin staining was observed in neuroblastoma, small cell lung cancer and melanoma. Malignant cell staining was strongest in neuroblastoma, weak in melanoma and rare in small cell lung cancer. In human cell lines, endosialin was detected in neuroblastoma cell lines, including cancer stem cell-like side population (SP) cells, but was absent in melanoma and was both rare and weak in small cell lung cancer. Human neuroblastoma xenograft tumors were found to be positive for endosialin. Our work suggests that endosialin may be a suitable therapeutic target for neuroblastoma.

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Section: Discussionsupporting

confidence: 63%

Endosialin: A novel malignant cell therapeutic target for neuroblastoma

Rouleau¹,

Smale²,

Sancho³

et al. 2011

Int J Oncol

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“…With a consortium of laboratories in the United States and abroad, the program is able to quickly screen a large number of agents using in vitro and in vivo models. (65,(69)(70)(71) The in vitro models are cell lines, with the in vivo models typically human patient-derived tumors grown as heterotopic xenografts in severe combined immunodeficiency mice. Although osteosarcoma can be grown in orthotopic as well as heterotopic sites, the heterotopic site permits frequent tumor size measurements using a caliper, which is feasible and cost-effective.…”

Section: Preclinical Screeningmentioning

confidence: 99%

“…This program has generated a large amount of data, including characterizations of the model systems, that has rapidly been published or made available through Web-based applications (http://home.ccr.cancer.gov/oncology/oncogenomics/). (65,(69)(70)(71) Canine Models…”

Section: Preclinical Screeningmentioning

confidence: 99%

Osteosarcoma

Görlick

Khanna

2010

Journal of Bone and Mineral Research

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152

126

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It has been difficult to identify the molecular features central to the pathogenesis of osteosarcoma owing to a lack of understanding of the cell or origin, the absence of identifiable precursor lesions, and its marked genetic complexity at the time of presentation. Interestingly, several human genetic disorders and familial cancer syndromes, such as Li-Fraumeni syndrome, are linked to an increased risk of osteosarcoma. Association of these same genetic alterations and osteosarcoma risk have been confirmed in murine models. Osteosarcoma is associated with a variety of genetic abnormalities that are among the most commonly observed in human cancer; it remains unclear, however, what events initiate and are necessary to form osteosarcoma. The availability of new resources for studying osteosarcoma and newer research methodologies offer an opportunity and promise to answer these currently unanswered questions. Even in the absence of a more fundamental understanding of osteosarcoma, association studies and preclinical drug testing may yield clinically relevant information. ß

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“…Current genomewide molecular-profiling studies indicate the retention of molecular characteristics that define tumor type. The recent study by Whiteford and colleagues 12 demonstrates that, by unsupervised clustering analysis of cDNA-expression profiles, xenografts derived from a histology can cluster accurately with their human counterparts. Similarly, direct comparison of patient tumor biopsy tissue with early-passage xenografts demonstrates high concordance in gene expression and even greater similarity in genomic alterations when tumors are propagated in mice.…”

Section: Introductionmentioning

confidence: 99%