Abstract
Human RNASET2 acts as a powerful oncosuppressor protein in in vivo xenograft-based murine models of human cancer. Secretion of RNASET2 in the tumor microenvironment seems involved in tumor suppression, following recruitment of M1-polarized macrophages. Here, we report a murine Rnaset2-based syngeneic in vivo assay. BALB/c mice were injected with parental, empty vector-transfected or murine Rnaset2-overexpressing mouse C51 or TS/A syngeneic cells and tumor growth pattern and immune cells distribution in tumor mass were investigated. Compared to control cells, mouse Rnaset2-expressing C51 cells showed strong delayed tumor growth. CD86+ M1 macrophages were massively recruited in Rnaset2-expressing C51-derived tumors, with concomitant inhibition of MDSCs and CD206+ M2 macrophages recruitment. At later times, a relevant expansion of intra-tumor CD8+ T cells was also observed. After re-challenge with C51 parental cells, most mice previously injected with Rnaset2-expressing C51 cells still rejected C51 tumor cells, suggesting a Rnaset2-mediated T cell adaptive immune memory response. These results point at T2 RNases as evolutionary conserved oncosuppressors endowed with the ability to inhibit cancer growth in vivo through rebalance of intra-tumor M1/M2 macrophage ratio and concomitant recruitment of adaptive anti-tumor CD8+ T cells.
Highlights
The human RNASET2 gene encodes for an evolutionarily conserved, pleiotropic extracellular ribonuclease, whose secretion by cancer cells in the tumor microenvironment (TME) is likely involvedCancers 2020, 12, 717; doi:10.3390/cancers12030717 www.mdpi.com/journal/cancersCancers 2020, 12, 717 in tumor suppression
In light of the previously mentioned role of human RNASET2 in modulating the macrophage activation/polarization state, to further investigate the oncosuppressive role of T2 Ribonucleases in the context of a completely immunocompetent experimental model we report here the in vivo role of the murine Rnaset2 gene by overexpressing it in either mammary adenocarcinoma-derived TS/A
Murine parental TS/A breast adenocarcinoma (TS/A P) and C51 colon carcinoma (C51 P) cells were first investigated by western blot analysis to assess their endogenous expression level of Rnaset2
Summary
The human RNASET2 gene encodes for an evolutionarily conserved, pleiotropic extracellular ribonuclease, whose secretion by cancer cells in the tumor microenvironment (TME) is likely involvedCancers 2020, 12, 717; doi:10.3390/cancers12030717 www.mdpi.com/journal/cancersCancers 2020, 12, 717 in tumor suppression. Two independent in vivo xenograft-based murine models of human ovarian cancer have been previously used to demonstrate a marked RNASET2-mediated in vivo tumor suppression [1,2]. Human RNASET2 overexpression in two independent human ovarian cancer cell lines, followed by challenging of immunodeficient mouse models with these cells, showed a marked tumor suppressive effect coupled with a RNASET2-mediated recruitment of M1-polarized host macrophages within the tumor mass [1,2]. These data, coupled to the well-established notion of T2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
