Human Recombinant Truncated RNASET2, Devoid of RNase Activity; A Potential Cancer Therapeutic Agent

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Nov 27

PMID 25426551

Citations 6

Authors

Liron Nesiel-Nuttman

Betty Schwartz

Oded Shoseyov

Affiliations

Soon will be listed here.

Abstract

Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors. Immunofluorescence staining of HUVECs showed nuclear and cytosolic RNASET2 protein that was no longer detectable inside the cell following trT2-50 treatment. This effect was associated with disruption of the intracellular actin network. trT2-50 co-localized with angiogenin, suggesting that both molecules bind (or compete) for similar cellular epitopes. Moreover, trT2-50 led to a significant inhibition of tumor development. Histological analysis demonstrated abundant necrotic tissue and a substantial loss of endothelial structure in trT2-50-treated tumors. Collectively, the present results indicate that trT2-50, a molecule engineered to be deficient of its catalytic activity, still maintained its actin binding and anticancer-related biological activities. We therefore suggest that trT2-50 may serve as a potential cancer therapeutic agent.

Citing Articles

RNase T2 in Inflammation and Cancer: Immunological and Biological Views.

Wu L, Xu Y, Zhao H, Li Y Front Immunol. 2020; 11:1554.

PMID: 32903619 PMC: 7438567. DOI: 10.3389/fimmu.2020.01554.

Ping-Pong-Tumor and Host in Pancreatic Cancer Progression.

Mu W, Wang Z, Zoller M Front Oncol. 2020; 9:1359.

PMID: 31921628 PMC: 6927459. DOI: 10.3389/fonc.2019.01359.

The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy.

Mironova N, Patutina O, Brenner E, Kurilshikov A, Vlassov V, Zenkova M Oncotarget. 2017; 8(45):78796-78810.

PMID: 29108266 PMC: 5667999. DOI: 10.18632/oncotarget.20228.

Guidance of Signaling Activations by Cadherins and Integrins in Epithelial Ovarian Cancer Cells.

Roggiani F, Mezzanzanica D, Rea K, Tomassetti A Int J Mol Sci. 2016; 17(9).

PMID: 27563880 PMC: 5037667. DOI: 10.3390/ijms17091387.

Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization.

Nesiel-Nuttman L, Doron S, Schwartz B, Shoseyov O Oncoscience. 2015; 2(1):31-43.

PMID: 25815360 PMC: 4341462. DOI: 10.18632/oncoscience.100.

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