Cited by 297Veterinary Oncology ResearchSarcoma Diagnosis and TreatmentHuman-Animal Interaction Studies

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression

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Paoloni, Melissa, Davis, Sean, Lana, Susan, Withrow, Stephen, Sangiorgi, Luca, Picci, Piero, Hewitt, Stephen, Triche, Timothy +2 more·2009·BMC Genomics

Abstract

BACKGROUND: Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. RESULTS: Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (IL-8) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (SLC1A3), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of IL-8 and SLC1A3 protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways. CONCLUSIONS: Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.

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  • The integrated canine approach has been particularly promising for evaluating anti-metastatic and immune-based therapeutics.

    “This integrated approach has been particularly promising for the evaluation of anti-metastatic 99,234 and immune-based therapeutics 69,235 .”

    From Osteosarcoma (2022) · cites this paper as [234]

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Authors
Paoloni, M., Davis, S., Lana, S., Withrow, S., Sangiorgi, L., Picci, P., Hewitt, S., Triche, T., Meltzer, P., & Khanna, C.
Affiliations
  • National Institutes of Health (US)
  • Colorado State University (US)
  • Istituto Ortopedico Rizzoli (IT)
  • University of Southern California (US)
Corresponding author
Paoloni, Melissa
Venue
BMC Genomics
Published
2009
Volume
10
Issue
1
Pages
625
ISSN
1471-2164 (ISSN-L)
OpenAlex
W2116599555
Cited by
291
References
52
Citations by year
2026: 10 · 2025: 18 · 2024: 13 · 2023: 24 · 2022: 15 · 2021: 22 · 2020: 32 · 2019: 16 · 2018: 17 · 2017: 11 · 2016: 18 · 2015: 18 · 2014: 17 · 2013: 13 · 2012: 19
FWCI
13.23
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Colorado State University
  • National Human Genome Research Institute
  • National Cancer Institute
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Veterinary Oncology Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Human-Animal Interaction Studies
Keywords
canine osteosarcoma, pediatric osteosarcoma, lung metastasis, comparative oncology, cross-species gene expression, interleukin-8, GLAST, prognostic factors, orthologs
MeSH terms
Animals, Child, Dogs, Humans, RNA, Neoplasm, Osteosarcoma, Cluster Analysis, Interleukin-8, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genomics, Excitatory Amino Acid Transporter 1, Cell Line, Tumor, Comparative Genomic Hybridization

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