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Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with a poor prognosis due to late diagnosis and loco-regional metastasis. Partial or more complete epithelial–mesenchymal transition (EMT) plays a role in tumor progression; however, it remains a challenge to observe the EMT in vivo, due to its transient nature. Here, we developed a novel catulin promoter-based reporter system that allows us to isolate and characterize in vivo a small fraction of invasive cancer cells. The analyses of tumors revealed that Catulin-green fluorescent protein (GFP)-positive cells were enriched in clusters of cells at the tumor invasion front. A functional genomic study unveiled genes involved in cellular movement and invasion providing a molecular profile of HNSCC invasive cells. This profile overlapped partially with the expression of signature genes related to the partial EMT available from the single cell analysis of human HNSCC specimens, highlighting the relevance of our data to the clinical disease progression state. Interestingly, we also observed upregulations of genes involved in axonal guidance—L1 cell adhesion molecule (L1CAM), neuropilin-1, semaphorins, and ephrins, indicating potential interactions of cancer cells and neuronal components of the stroma. Taken together, our data indicated that the catulin reporter system marked a population of invasive HNSCC cells with a molecular profile associated with cancer invasion.

Catulin Based Reporter System to Track and Characterize the Population of Invasive Cancer Cells in the Head and Neck Squamous Cell Carcinoma