Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Pathology

AUTOCRINE AND PARACRINE REGULATION OF METASTATIC GROWTH IN CANINE OSTEOSARCOMA
Dafydd G. Thomas¹, Kirsten M. Leu², Stephen Hewitt³, Chand Khanna³, Lee Helman³, Thomas J. Giordano¹, Laurence Baker²
¹Department of Pathology University of Michigan Hospitals, ²Division of Hematology & Oncology Department of Internal Medicine University of Michigan Hospitals, ³Pediatric Oncology Branch NCI, NIH

OBJECTIVE: Canine osteosarcoma is a naturally occurring tumor homologous to their human tumors in morphology and behavior. Consequently the canine neoplasm is a useful model to test new disease modifying agents. Recently, the treatment of other mesenchymal tumors using anti-tyrosine kinase drugs, especially drugs targeted against the PDGF family has been proposed. The PDGF family consists of 3 dimeric proteins, which act as ligands for the 2 receptors (PDGFR-a and PDGFR-b) with tyrosine kinase activity. The dimers are formed by subunits A and B can bind as the heterodimer or the homodimers. PDGF-B is similar to proto-oncogene c-sis, which is involved in the malignant transformation of fibroblast cultures. The a receptor is stimulated by all three isoforms of the ligand, whereas the b-receptor only binds the PDGF-B homodimer with high affinity.

METHODS: In this study, the expression of the PDGF family members in 84 canine osteosarcomas (73 primary and 11 pulmonary metastatic neoplasms) was examined using a tissue microarray and immunohistochemistry.

RESULTS: PDGF-A and PDGF-B expression was detected in 43 (51%) and 8 tumors (9.5%) respectively. 66 tumors (78.5%) expressed PDGFR-a and 52 tumors (61.9%) expressed PDGFR-b respectively. Concomitant expression of the ligand (PDGF-A and PDGF-B) and receptor (PDGFR-a) was seen in all of the metastatic lesions, whereas primary neoplastic lesions demonstrated likewise concomitant expression in 27 lesions (36%).

CONCLUSION: These results suggest autocrine and paracrine stimulation of osteosarcoma cells in metastatic lesions. Furthermore, these results suggest metastatic osteosarcoma may be a possible target for anti-PDGFR drugs.