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Investigating TrkA expression in canine appendicular osteosarcoma.

T M Fan¹, A M Barger, I T Sprandel

¹Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802-4714, USA. t-fan@uiuc.edu

Journal of Veterinary Internal Medicine

|July 22, 2008

Summary

Canine osteosarcoma cells express TrkA, a receptor tyrosine kinase. Blocking TrkA signaling induces apoptosis, suggesting TrkA antagonists may treat canine osteosarcoma.

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Area of Science:

Oncology
Molecular Biology
Veterinary Medicine

Background:

The tropomyosin-related kinase A (TrkA) receptor tyrosine kinase binds nerve growth factor (NGF).
TrkA signaling is crucial for neuronal development and survival.
TrkA is also expressed in osteoblasts, where it promotes survival.

Purpose of the Study:

To determine if canine osteosarcoma (OSA) cells express TrkA.
To investigate the role of TrkA signaling in canine OSA cell mitogenesis and survival.

Main Methods:

TrkA expression was assessed in canine OSA cell lines and tumor samples using RT-PCR, flow cytometry, and immunohistochemistry.
In vitro assays evaluated the impact of TrkA signaling on cell proliferation and survival.
In vivo analysis examined TrkA expression in primary tumors and metastases.

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Main Results:

Canine OSA cells express TrkA mRNA and protein.
Blocking TrkA signaling induced apoptosis in canine OSA cell lines.
TrkA protein was detected in most primary canine OSA tumors and metastatic lesions.

Conclusions:

Canine osteosarcoma cells express TrkA, and its signaling pathway confers protection against apoptosis.
The presence of TrkA in canine OSA tumors and metastases suggests TrkA antagonists as a potential therapeutic strategy.