Publikationsdatenbank

Cellular crosstalk between canine fibroblasts and a mast cell tumour cell line and its significance in fibroblast activation (2020)

Art

Hochschulschrift

Autor

Aguilera Rojas, Matias Ignacio (WE 3)

Quelle

Berlin: Mensch und Buch Verlag Berlin, 2020 — VIII, 74 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/28361

Kontakt

Institut für Veterinär-Biochemie

Oertzenweg 19 b
14163 Berlin
+49 30 838 62225
biochemie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Naturally occurring cancers are the most common cause of death in dogs. Tumours represent complex interactive systems that combine different cell types and non-cellular elements. All components of the tumoral niche and their dynamic interactions comprise the tumour microenvironment (TME). Within the TME, fibroblasts are of significant interest as they are reprogrammed by cancer cells into cancer-associated fibroblasts (CAFs), which then further promote the abnormal growth and division of cancer cells. Various cancer-derived biomolecules including growth factors, cytokines, and microRNAs (miRNAs) have been reported to induce CAF activation. Exosomes transport an assorted biological cargo that plays an essential role in mediating the intercellular crosstalk within the TME. In this context, cancer cell-derived exosomes are specially enriched in miRNAs, which can trigger CAF differentiation and regulate cancer progression by targeting tumour suppressors or oncogenes. Moreover, dysregulation of miRNAs has been proposed as an emerging hallmark of cancer, both in the tumour itself and within the TME. Interestingly, known biochemical pathways involved in carcinogenesis in humans are also frequently deregulated in canine neoplasms. The essential similarities between canine and human genetic mechanisms for carcinogenesis make translational and comparative studies especially valuable and beneficial for both species. This study initially detected that canine primary dermal fibroblasts and the mast cell tumour cell line C2 are each capable of releasing exosomes into the cell culture media under standard culture conditions. Then, from a targeted miRNA approach, the aim was to better understand how resting fibroblasts can be activated by cancer cells. To do so, the effects of intercellular communication between canine fibroblasts and C2 cells were investigated via coculture of both types of cells and by culturing fibroblasts with purified C2 exosomes. The results suggest that canine dermal fibroblasts are activated by C2 cells via intercellular crosstalk involving miRNA dysregulation, which may further support tumour cell proliferation. Additional RNA interference-mediated knockdown experiments provide evidence that miR-27a alone can influence the expression of proteins associated with fibroblast activation. Namely, downregulation of miR-27a in canine tumours may take part in the remodelling process of the TME by controlling the expression of its cancer-associated target genes. These findings are comparable to data obtained from studies already performed on the human system, which further supports the notion of the domestic dog as a suitable animal model within the field of miRNA crosstalk and cancer research.