Rac1 signaling-associated genes are upregulated in nodal metastasis of canine oral mucosal melanoma

Oral mucosal melanomas (OMMs) are the most frequent oral malignancy in dogs, often characterized by aggressive local behavior and a high metastatic rate. The mechanisms that drive canine OMM metastasis are still largely unknown, providing for limited therapeutic approaches once the disease has spread to metastatic sites. The objective of this investigation was to evaluate the differences in gene expression between canine primary OMMs and their matched nodal metastases. Transcriptional profiling of formalin-fixed, paraffin-embedded biopsies of 4 canine OMMs and their respective lymph node biopsies was performed using exon microarrays. Confirmation of the differential expression of selected genes was subsequently sought by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) on 13 paired samples (primary tumor-metastatic lymph node). Results highlight the activation of pathways associated with actin cytoskeleton organization, and cellular motility and migration. In particular, transcriptional data indicated increased expression of genes associated with Rac1 signaling-regulated cell migration, including ELMO1, VAV3, and DOCK2, in nodal metastases. Overall, the results of this investigation point to a significant role for Rac1 signaling in the pathogenesis of OMM metastasis to regional lymph nodes. The Rac1 signaling-associated genes highlighted herein are indeed involved in the activation of cellular migration, and one, or more, may represent a future therapeutic target to prevent metastatic dissemination, or treat OMM with distant metastases.