Transcriptomic profile reveals molecular events associated to focal adhesion and invasion in canine mammary gland tumour cell lines

Abstract

The prevalence of cancer in animals has increased significantly over the years. Mammary tumours are the most common neoplasia in dogs, in which around 50% are presented in the malignant form. Hence, the development and characterization of in vitro models for the study of canine tumours are important for the improvement of cancer diagnosis and treatment. Thus, the aim of this study was to characterize cell lines derived from canine mammary gland neoplasias which could be further used for basic and applied oncology research. Samples of canine mammary carcinomas were taken for cell culture and 2 cell lines were established and characterized in terms of cell morphology, tumourigenicity and global gene expression. Both cell lines presented spindle-shape morphology and shown common malignant features as in vitro invasion potential and expression of epithelial and mesenchymal proteins. Also, we found gene expression patterns between the 2 cell cultures in comparison to the normal mammary gland tissue. Cells from M25 culture showed a higher invasion and in vivo tumourigenic potential, associated to the overexpression of genes involved in focal adhesion and extracellular matrix communication, such as FN1, ITGA8 and THBS2. The phenotypic characterization of these cells along with their global gene expression profile potentially determine new therapeutic targets for mammary tumours.

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines with Vasculogenic Mimicry Ability <em>in vitro</em> and <em>in vivo</em>

“…The difference in cell doubling time is expected as these are different tumours. These results are similar to those found by Cordeiro et al [24] in which the doubling times of two different cells lines cultured in vitro were 26 and 42 hours and, in this case, one cell line was more malignant than other.…”

ZEB1 and ZEB2 transcription factors are potential therapeutic targets of canine mammary cancer cells

“…First, the five cell lines were analysed morphologically and by expression of intermediate filaments. Four cell lines were previously established in our laboratory showing a mesenchymal‐like (M5 and M25) or epithelial‐like phenotype (E20 and E37). In addition, a commercial established cell line (CF41.Mg) was used in this work showing a mesenchymal‐like morphology (Figure ).…”

“…Five CMC cell lines were used in this study, where four were isolated and characterized in our laboratory, as previously described . Two of these cells presented an epithelial‐like morphology (E20 and E37) and two a mesenchymal‐like morphology (M5 and M25).…”

“…The first is determined by the ability of cancer cells to generate new tumors, while the second is the capacity to invade the extracellular matrix (ECM) to disseminate through the blood or lymphatic vessels and colonize a secondary tissue, generating metastasis . Recently, our group showed that the overexpression of genes involved in focal adhesion and ECM communication (FN1, ITGA8 and THBS2) is associated with invasiveness and in vivo tumorigenesis of canine mammary cancer (CMC) cell lines . However, the identification of master regulators of these phenotypes is crucial to develop novel therapeutic targets.…”

“…6 Recently, our group showed that the overexpression of genes involved in focal adhesion and ECM communication (FN1, ITGA8 and THBS2) is associated with invasiveness and in vivo tumorigenesis of canine mammary cancer (CMC) cell lines. 7 However, the identification of master regulators of these phenotypes is crucial to develop novel therapeutic targets.…”