Intercellular interactions between mast cells and stromal fibroblasts obtained from canine cutaneous mast cell tumours

Abstract

Mast cell tumours (MCTs) are the most frequent malignant skin neoplasm in dogs. Due to the difficulty in purifying large numbers of canine neoplastic mast cells, relatively little is known about their properties. A reproducible in vitro model is needed to increase the understanding about the phenotype and functional properties of neoplastic mast cells. In the present study, we describe the establishment of primary cocultures of neoplastic mast cells from canine cutaneous MCTs and cancer-associated fibroblasts. We confirmed the inability of canine neoplastic mast cells to remain viable for long periods in vitro without the addition of growth factors or in vivo passages in mice. Using a transwell system, we observed that mast cell viability was significantly higher when there is cell-to-cell contact in comparison to non-physical contact conditions and that mast cell viability was significantly higher in high-grade than in low-grade derived primary cultures. Moreover, the use of conditioned medium from co-cultured cells led to a significantly higher tumoral mast cell viability when in monoculture. Signalling mechanisms involved in these interactions might be attractive therapeutic targets to block canine MCT progression and deserve more in-depth investigations.

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cultures grown in a repeatable system

“…More so, 3D systems allowing interactions between the tumor microenvironment and the corresponding neoplastic cells have proven essential in designing experimental approaches to personalized medicine and predicting the effect of different drugs also in dogs. [11,18,20] The study of speci c canine tumors is considered useful as they represent spontaneous models for the human counterparts. Compared to xenograft or genetically modi ed murine models, the dog shares with humans more than ~ 650 Mb of ancestral sequences; furthermore, canine DNA and protein sequences are more similar to humans compared to rodents.…”

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cell cultures grown in a repeatable system—preliminary results

“…These studies have demonstrated the better performances and the essential role of 3D culture systems for the understanding of treatment response and the emergence of chemo-resistant clones. More so, 3D systems allowing interactions between the tumor microenvironment and the corresponding neoplastic cells have proven essential in designing experimental approaches to personalized medicine and predicting the effect of different drugs also in dogs [ 11 , 18 , 20 ].…”