Characterizing Monocyte-Dependent Gene Expression in Metastatic Canine Osteosarcoma
Dwyer, Noah
2023-12-01
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While metastasis of canine osteosarcoma (OS) predominantly occurs in the lungs, it also develops in subcutaneous tissue, kidneys, and other bones. A role for CCR2 and IL-8 in OS pulmonary metastasis has been identified, but it is unknown whether monocytes play an equally important role in driving the metastatic behavior of OS to alternate metastatic sites. NanoString nCounter analysis of gene ... read moreexpression was performed in primary and multiple matched metastatic lesions (lung, kidney, subcutaneous, bone) and identified a predominance of monocyte associated gene signatures in lung and renal sites when compared to subcutaneous and bone sites. It was therefore hypothesized that monocyte infiltrates are present in renal metastases and that monocyte-associated immunosuppressive gene expression signatures are conserved across patient-matched pulmonary and renal metastatic samples. It was further hypothesized that robust monocyte infiltrates are not present in subcutaneous or bone metastases. The NanoString GeoMX Digital Spatial Profiler was used to analyze and compare the transcriptomes of patient matched OS metastatic samples collected from dogs and prepared on TMAs. Fluorescent conjugated morphologic antibodies targeting nuclei, vimentin, CD3 T-cells and macrophages were used to guide region of interest selection and to separate monocyte infiltrates from surrounding cell populations. The GeoMx Canine Cancer Panel was hybridized to each slide allowing for analysis of differential expression of genes within selected regions of varying monocyte density at each metastatic site. These findings will help to characterize the role of monocytes in driving OS metastatic behavior in alternate metastatic sites.
Cummings School of Veterinary Medicine Student Summer Research 2023.read less - ID:
- 44558v358
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