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

Melissa Paoloni, Sean Davis, Susan Lana, Stephen Withrow, Luca Sangiorgi, Piero Picci, Stephen Hewitt, Timothy Triche, Paul Meltzer, Chand Khanna

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)625
Number of pages1
JournalBMC Genomics
Volume10
DOIs
Publication statusPublished - 2009

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Osteosarcoma
Genomics
Canidae
Neoplasms
Pediatrics
Neoplasm Metastasis
Interleukin-8
Dogs
Dog Diseases
Amino Acid Transport System X-AG
Pets
Oligonucleotide Array Sequence Analysis
Neuroglia
Cluster Analysis
Cause of Death
Gene Expression
Lung
Survival

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression. / Paoloni, Melissa; Davis, Sean; Lana, Susan; Withrow, Stephen; Sangiorgi, Luca; Picci, Piero; Hewitt, Stephen; Triche, Timothy; Meltzer, Paul; Khanna, Chand.

In: BMC Genomics, Vol. 10, 2009, p. 625.

Research output: Contribution to journalArticle

Paoloni, M, Davis, S, Lana, S, Withrow, S, Sangiorgi, L, Picci, P, Hewitt, S, Triche, T, Meltzer, P & Khanna, C 2009, 'Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.', BMC Genomics, vol. 10, pp. 625. https://doi.org/10.1186/1471-2164-10-625
Paoloni, Melissa ; Davis, Sean ; Lana, Susan ; Withrow, Stephen ; Sangiorgi, Luca ; Picci, Piero ; Hewitt, Stephen ; Triche, Timothy ; Meltzer, Paul ; Khanna, Chand. / Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression. In: BMC Genomics. 2009 ; Vol. 10. pp. 625.
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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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N2 - 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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