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Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
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Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma.

Stephanie Goldschmidt1, Clifford G Tepper2, Jack Goon3

  • 1Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.

Molecular Carcinogenesis
|June 17, 2025
PubMed
Summary

This study maps the canine oral squamous cell carcinoma (COSCC) transcriptome, revealing distinct molecular signatures across tumor regions and the microenvironment. Findings identify potential biomarkers for malignancy and therapeutic targets, offering insights for comparative human cancer research.

Keywords:
head and neck squamous cell carcinomaoral canceroral dysplasiaoral squamous cell carcinomatranscriptomics

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Area of Science:

  • Veterinary Oncology
  • Comparative Pathology
  • Cancer Genomics

Background:

  • Canine oral squamous cell carcinoma (COSCC) is a prevalent tumor in dogs, serving as a valuable model for human oral cancer research.
  • Previous genomic studies on COSCC relied on bulk sequencing, limiting spatial and molecular resolution.
  • Understanding the transcriptomic landscape of COSCC is crucial for identifying biomarkers and therapeutic targets.

Purpose of the Study:

  • To comprehensively analyze the transcriptomic landscape of COSCC with spatial resolution.
  • To compare molecular signatures of tumor regions, peritumoral dysplasia, and the tumor microenvironment with normal oral tissues.
  • To identify potential biomarkers for malignancy and therapeutic targets.

Main Methods:

  • Spatial transcriptomics analysis of COSCC samples, including surface tumor, deep invasive tumor, peritumoral dysplastic epithelium, and tumor microenvironment.
  • Comparison with matched normal oral samples.
  • Gene set enrichment analysis and identification of differentially expressed genes.

Main Results:

  • Distinct molecular signatures were observed in different regions of COSCC.
  • Genes associated with epithelial growth factor (EGFR) and epithelial-mesenchymal transformation (EMT) were upregulated in dysplasia and surface cancer.
  • Specific gene signatures for dysplastic lesions (FZD4, GAS1, HACD2, NOG, SLC39A6) and invasive COSCC (SFRP4, FZD1, IL34) were identified.
  • The tumor microenvironment showed increased macrophages, IL-10 secretion, and CD4+ T-cells expressing both stimulatory (ICOS) and inhibitory (CTLA4) molecules, suggesting immune suppression.

Conclusions:

  • This study provides a detailed transcriptomic map of COSCC, highlighting regional molecular differences.
  • Identified genes offer potential as biomarkers for malignancy, prediction of tumor behavior, and novel therapeutic targets.
  • The immunomodulatory tumor microenvironment, particularly high CTLA4 expression, suggests a suppressed anti-tumor immune response that warrants further investigation.