Global Gene Expression Analysis of Canine Osteosarcoma Stem Cells Reveals a Novel Role for COX-2 in Tumour Initiation
Year: 2014
Type: article
Abstract: Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.
Source: PLoS ONE
Language: English
Topic: Veterinary Oncology Research
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: Development and exploitation of animal biotechnologies, National Capability Grant - Edinburgh Genomics, Stem cell biology - Ageing, Developmental Biology, Genetically Modified Animals, Stem Cells, The 3Rs, Tissue damage and repair - Animal Diseases, Genetically Modified Organisms, Regenerative Medicine, Underpinning Cancer Research, Stem Cells, Tissue and organ development in the intact animal - Agriculture, Animal Welfare, Developmental Biology, Diet and Health , Genetically Modified Organisms, Characterisation of primitive stem cell-like canine cancer cells: identification of therapeutic targets through genomics, Regulatory networks in development - Animal Diseases, Developmental Biology, Genomic Proteomics and Metabolomics, Systems Biology, Stem Cells
OpenAlex ID: W1995370402