Project description:Tumors frequently found in dogs include canine oral tumors, either cancerous or noncancerous. The bloodstream is an important route for tumor metastasis, particularly for late-stage oral melanoma (LOM) and late-stage oral squamous cell carcinoma (LOSCC). The present study aimed to investigate serum peptidome-based biomarkers of dogs with early-stage oral melanoma, LOM, LOSCC, benign oral tumors, chronic periodontitis and healthy controls, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry.
Project description:Common overexpressing genes were identified in all human oral squamous cell carcinoma tissues and/or cultured cells. Ten oral squamous cell carcinoma tissues and 10 human oral squamous cell carcinoma cell lines were analyzed. Three normal oral mucosa tissues and a human non-neoplastic keratinocyte cell lines were used as control samples.
Project description:Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial–mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.
Project description:Predictive Value of MicroRNAs in the Progression of Oral Leukoplakias Comparison of 10 samples from non-progressive leukoplakias (did not turn into oral squamous cell carcinoma), with 10 samples from progressive leukoplakias (turned into oral squamous cell carcinoma w/in 5 yrs)
Project description:The baseline immune landscape of spontaneous canine HNSCC tumors was asssessed using immunohistochemistry and nanostring gene expression profiling of 34 canine oral carcinoma tumors and two normal oral mucosal tissue samples.
Project description:Epithelial-mesenchymal plasticity (EMP) is a cellular process activated in carcinoma cells to drive invasiveness, metastasis, and chemoresistance. Recently, we have demonstrated that activation of the EMP program also results in the assembly of an immunosuppressive tumor microenvironment and resistance to immunotherapy in an immunocompetent orthotopic murine model. However, it has yet to be shown whether these findings can be translated to canine carcinomas. Here, we show that in spontaneous canine mammary carcinomas (CMCs), which share similar histopathologic, molecular, and clinical features with human breast cancers, EMP activation is linked to the recruitment of immunosuppressive cells including regulatory T-cells and M2-like macrophages. Additionally, through transcriptomic profiling of CMCs, we identify that the glycoprotein CD109 is associated with EMP-mediated immunosuppression across canine, murine, and human breast cancer models. CD109 has been previously associated with tumorigenicity, but not immunosuppression in cancers of any species. Finally, we identified upregulation of several immunosuppressive paracrine factors across multiple canine carcinomas, including oral squamous cell carcinoma, urothelial carcinoma, and pulmonary carcinoma samples. These findings demonstrate for the first time that the EMP program is associated with immunosuppression in canine carcinomas, with direct translational implications for human breast cancers.
Project description:micro-RNA in cancer-associated fibroblasts in oral squamous cell carcinoma vs. dysplasia-associated fibroblasts from dysplastic oral lesions vs. normal fibroblasts from normal oral mucosa from healthy individual.