Evaluation of Serum Level of Chemokine (C-C Motif) Ligand 2 (CCL2) in Canine Urothelial Carcinomas, Mast Cell Tumours, and Insulinomas, and Its Correlation With Circulating Monocytes.

Abstract

Chemokine (C-C motif) ligand 2 (CCL2) is a strong monocyte chemoattractant that has been shown to be increased in humans and dogs with neoplasia. Although in human urothelial carcinoma (UCa) CCL2 levels increase with metastatic disease, a previous study showed an opposite trend in dogs. The aim of this study was to assess serum CCL2 levels in dogs with mast cell tumours (MCT) and insulinoma with or without metastasis. The second aim was to evaluate any correlation between CCL2 serum levels and circulating monocyte counts in UCa, MCT and insulinoma. Serum CCL2 levels were significantly higher in dogs affected with MCT or insulinoma compared to healthy dogs (p = 0.002 and p = 0.017, respectively). Furthermore, low levels of serum CCL2 were associated with metastasis in insulinoma-affected dogs (p = 0.04) similarly to UCa-affected dogs. However, in the MCT group, low levels of serum CCL2 were associated with non-metastatic disease (p = 0.0045). Based on receiver operating characteristic (ROC) curves, optimal cut-off values were determined for CCL2 concentration in order to calculate sensitivity and specificity of the test. Good accuracy was reached for CCL2 as a diagnostic marker, but it was poor as a staging marker. In conclusion, a dual role of CCL2 has been shown in different tumour types. A low level of CCL2 was associated with metastatic disease in dogs with insulinoma similarly to UCa-affected dogs. In contrast, a low level of CCL2 was associated with a non-metastatic disease in dogs with MCT. There was only a moderate correlation between CCL2 and circulating monocyte count in our study in both Uca and MCT, and a fair opposite correlation in insulinoma, leading to hypothesise that the influx of monocytes may be better observed in the tumour itself rather than in the circulation. These results could help to further understand CCL2 in the tumour microenvironment and its possibility as a therapeutic target.