Do alterations in gene expressions influence tumorigenesis in the transmissible venereal tumor in dogs?

Abstract

Canine transmissible venereal tumor (CTVT) is a transmissible neoplasm, which spreads naturally between dogs through the halogenic transfer of tumor cells, mainly during coitus. It is the oldest known tumoral lineage in nature and reports on gene mutations have been extended. Also, this tumor shares several genetic mutations with some cancers in humans, among them lung carcinomas, melanoma, prostate, breast, among other cancers. Thus, expression of tumor suppressor genes such as TP53, P21, and apoptosis-related genes such as BAX, BCL-2, and BCL-xL, both in vivo and in vitro (primary cell culture) were quantified. In the present study, the comparison of gene expression, the TP53 gene, in most cases, was shown to be high in the majority of tissues (65%) and primary cell culture (100%), while BCL-2, BCL-xL, and BAX presented variation among the animals analyzed. Moreover, in these situations, the results suggested that the apoptotic regulation of these genes did not occur for TP53. The P21 gene was shown to be mostly normal (70%); although, absence (6%) and underexpressions (24%) were also observed. Statistical analysis of the BCL-xL gene demonstrated significant differences between the tissues of the animals when compared to the cell cultures; however, to the other genes, no statistical difference was observed between the groups. Preliminarily, the results suggested the presence of alterations in the gene expressions of the TP53, P21, BAX, BCL-2 and BCL-xL leading to loss of function in these genes, which affect the tumorigenesis of CTVT.

Immunophenotypic and molecular profile of cancer stem‐cell markers in ex vivo canine transmissible venereal tumour (CTVT)

“…However, a few studies have referred to the potential role of CD90 as a CSC marker in canine tissues. Low percentages of CD90 + cells in canine melanomas, osteosarcomas and hepatocellular carcinomas have been reported (Ailles & Weissman, 2007; Ballestero et al., 2020; Blacking et al., 2012; Buishand et al., 2016; Bustin et al., 2009; Calloni et al., 2013; Flórez et al., 2012; Greve et al., 2012; Guth et al., 2014; Huang et al., 2015; Ito et al., 2011; Kapoor et al., 2019; Kim & Ryu, 2017; Kulmann‐Leal et al., 2020; Livak & Schmittgen, 2001; Matou‐Nasri et al., 2009; Michishita et al., 2014; Mukaratirwa et al., 2004; Olofsson et al., 2014; Rege & Hagood, 2006; Savani et al., 2001; Su et al., 2015; Teye et al., 2016; Tirino et al., 2013; Wang et al., 2001; Yan et al., 2015; Yan et al., 2013; Yin et al., 1997; Yu & Stamenkovic, 2000; Zöller, 2015). Similarly, very low CD90 expression levels were found in the majority of CTVT tested in our study.…”

“…Although a few efforts towards MSC identification and extracellular matrix characterisation have been carried out for CTVT (Ballestero et al., 2020; Mukaratirwa et al., 2004), data on CD34 expression by MSC is currently non‐existent. Curiously, no stromal cells displayed CD34 staining in our study.…”

Could dysregulation of RASSF1 expression be a mechanism of tumorigenesis in CTVT?

“…Furthermore, the genome variation captured in global CTVT populations has highlighted some of the unique adaptations that have driven this lineage to become the longest-living and most prolific cancer known in nature (Strakova & Murchison 2015). In addition it provides an excellent research model for comparative oncology (Fêo et al 2020).…”

“…This work is part of a study that has already been published in the form of two articles that quantified: the expression of genes related to the immune system such as IL-6, IFN-γ, and TGF-β, as well as angiogenic factors (VEGF, CXCR4) (Fêo et al 2018), and the expression of tumor suppressor genes, such as TP53, P21, and apoptosis-related genes, such as BAX, BCL-2, and BCL-xL (Fêo et al 2020).…”