Evaluation of canonical Hedgehog signaling pathway inhibition in canine osteosarcoma.

Canine osteosarcoma (OSA), the most common canine primary bone malignancy, has a highly aggressive biologic behavior. Despite current standard of care therapies, including amputation and adjuvant chemotherapy, most dogs still succumb to metastatic disease. Further investigations into molecular mechanisms and pathways driving OSA are needed to improve therapeutic options.

met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable pre-clinical model of human osteosarcoma.

The Met receptor tyrosine kinase (RTK) is aberrantly expressed in human osteosarcoma and is an attractive molecular target for cancer therapy. We studied spontaneous canine osteosarcoma (OSA) as a potential pre-clinical model for evaluation of Met-targeted therapies. The canine MET oncogene exhibits 90% homology compared with human MET, indicating that cross-species functional studies are a viable strategy.

Protein kinase Cepsilon mediates polymeric fibronectin assembly on the surface of blood-borne rat breast cancer cells to promote pulmonary metastasis.

Malignant breast cancer cells that have entered the blood circulation from primary mammary fat pad tumors or are grown in end-over-end suspension culture assemble a characteristic, multi-globular polymeric fibronectin (polyFn) coat on their surfaces. Surface polyFn is critical for pulmonary metastasis, presumably by facilitating lung vascular arrest via endothelial dipeptidylpeptidase IV (CD26). Here, we show that cell-surface polyFn assembly is initiated by the state of suspension, is dependent upon the synthesis and secretion of cellular Fn, and is augmented in a dose- and time-dependent manner by plasma Fn.