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Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase.

Lualdi M, Pedrini E, Rea K, Monti L, Scaldaferri D, Gariboldi M, Camporeale A, Ghia P, Monti E, Tomassetti A, Acquati F, Taramelli R - Oncotarget (2015)

Bottom Line: Indeed, RNASET2 expression levels were consistently found to increase following stress induction.Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur.Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.

ABSTRACT
As widely recognized, tumor growth entails a close and complex cross-talk among cancer cells and the surrounding tumor microenvironment. We recently described the human RNASET2 gene as one key player of such microenvironmental cross-talk. Indeed, the protein encoded by this gene is an extracellular RNase which is able to control cancer growth in a non-cell autonomous mode by inducing a sustained recruitment of immune-competent cells belonging to the monocyte/macrophage lineage within a growing tumor mass. Here, we asked whether this oncosuppressor gene is sensitive to stress challenges and whether it can trigger cell-intrinsic processes as well. Indeed, RNASET2 expression levels were consistently found to increase following stress induction. Moreover, changes in RNASET2 expression levels turned out to affect several cancer-related parameters in vitro in an ovarian cancer cell line model. Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur. Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.

No MeSH data available.


Related in: MedlinePlus

RNASET2 affects several cancer-related parameters in OVCAR3 cells following chemically-induced hypoxiaA) A cell proliferation assay was performed in RNASET2-silenced (shRNASET2) and scrambled control OVCAR3 cell clones (Ctrl), following a 24-hours treatment with 100 μM CoCl2 (start in Day 0). RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. By contrast, RNASET2-silenced clones showed a proliferation rate significantly higher than control clones during recovery from chemical hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four ctrl OVCAR3 cell clones. B) A flow cytometry analysis was performed in RNASET2-silenced and scrambled control OVCAR3 cell clones stained with propidium iodide, following a 24-hours treatment with 100 μM CoCl2. C) RNASET2-silenced OVCAR3 cell clones generate a greater number of colonies than control cell clones in colony formation assay. Control clones, but not their RNASET2-silenced counterpart, were significantly affected in their clonogenic capability by CoCl2 treatment. D) RNASET2 significantly affects anchorage-independent growth in two-layer soft agar assay, in both normal culture conditions and chemically-induced hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four control OVCAR3 cell clones. Statistical analysis was performed using two-tailed Student's t-test. *p<0,05; **p<0,01; n.s.: not significant.
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Figure 3: RNASET2 affects several cancer-related parameters in OVCAR3 cells following chemically-induced hypoxiaA) A cell proliferation assay was performed in RNASET2-silenced (shRNASET2) and scrambled control OVCAR3 cell clones (Ctrl), following a 24-hours treatment with 100 μM CoCl2 (start in Day 0). RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. By contrast, RNASET2-silenced clones showed a proliferation rate significantly higher than control clones during recovery from chemical hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four ctrl OVCAR3 cell clones. B) A flow cytometry analysis was performed in RNASET2-silenced and scrambled control OVCAR3 cell clones stained with propidium iodide, following a 24-hours treatment with 100 μM CoCl2. C) RNASET2-silenced OVCAR3 cell clones generate a greater number of colonies than control cell clones in colony formation assay. Control clones, but not their RNASET2-silenced counterpart, were significantly affected in their clonogenic capability by CoCl2 treatment. D) RNASET2 significantly affects anchorage-independent growth in two-layer soft agar assay, in both normal culture conditions and chemically-induced hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four control OVCAR3 cell clones. Statistical analysis was performed using two-tailed Student's t-test. *p<0,05; **p<0,01; n.s.: not significant.

Mentions: First, we compared the in vitro cell proliferation rate of RNASET2-silenced (shRNASET2) clones to that of control clones (Ctrl) following a 24-hours treatment with 100 μM CoCl2 (Figure 3A). In unstressed cells, RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. However, under hypoxic conditions the proliferation rate of RNASET2-silenced clones was significantly higher when compared to controls during recovery from chemical hypoxia.


Pleiotropic modes of action in tumor cells of RNASET2, an evolutionary highly conserved extracellular RNase.

Lualdi M, Pedrini E, Rea K, Monti L, Scaldaferri D, Gariboldi M, Camporeale A, Ghia P, Monti E, Tomassetti A, Acquati F, Taramelli R - Oncotarget (2015)

RNASET2 affects several cancer-related parameters in OVCAR3 cells following chemically-induced hypoxiaA) A cell proliferation assay was performed in RNASET2-silenced (shRNASET2) and scrambled control OVCAR3 cell clones (Ctrl), following a 24-hours treatment with 100 μM CoCl2 (start in Day 0). RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. By contrast, RNASET2-silenced clones showed a proliferation rate significantly higher than control clones during recovery from chemical hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four ctrl OVCAR3 cell clones. B) A flow cytometry analysis was performed in RNASET2-silenced and scrambled control OVCAR3 cell clones stained with propidium iodide, following a 24-hours treatment with 100 μM CoCl2. C) RNASET2-silenced OVCAR3 cell clones generate a greater number of colonies than control cell clones in colony formation assay. Control clones, but not their RNASET2-silenced counterpart, were significantly affected in their clonogenic capability by CoCl2 treatment. D) RNASET2 significantly affects anchorage-independent growth in two-layer soft agar assay, in both normal culture conditions and chemically-induced hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four control OVCAR3 cell clones. Statistical analysis was performed using two-tailed Student's t-test. *p<0,05; **p<0,01; n.s.: not significant.
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Figure 3: RNASET2 affects several cancer-related parameters in OVCAR3 cells following chemically-induced hypoxiaA) A cell proliferation assay was performed in RNASET2-silenced (shRNASET2) and scrambled control OVCAR3 cell clones (Ctrl), following a 24-hours treatment with 100 μM CoCl2 (start in Day 0). RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. By contrast, RNASET2-silenced clones showed a proliferation rate significantly higher than control clones during recovery from chemical hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four ctrl OVCAR3 cell clones. B) A flow cytometry analysis was performed in RNASET2-silenced and scrambled control OVCAR3 cell clones stained with propidium iodide, following a 24-hours treatment with 100 μM CoCl2. C) RNASET2-silenced OVCAR3 cell clones generate a greater number of colonies than control cell clones in colony formation assay. Control clones, but not their RNASET2-silenced counterpart, were significantly affected in their clonogenic capability by CoCl2 treatment. D) RNASET2 significantly affects anchorage-independent growth in two-layer soft agar assay, in both normal culture conditions and chemically-induced hypoxia. Triplicate experiments were performed with four RNASET2-silenced and four control OVCAR3 cell clones. Statistical analysis was performed using two-tailed Student's t-test. *p<0,05; **p<0,01; n.s.: not significant.
Mentions: First, we compared the in vitro cell proliferation rate of RNASET2-silenced (shRNASET2) clones to that of control clones (Ctrl) following a 24-hours treatment with 100 μM CoCl2 (Figure 3A). In unstressed cells, RNASET2-silenced clones showed no difference in proliferation rate when compared to control clones. However, under hypoxic conditions the proliferation rate of RNASET2-silenced clones was significantly higher when compared to controls during recovery from chemical hypoxia.

Bottom Line: Indeed, RNASET2 expression levels were consistently found to increase following stress induction.Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur.Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.

View Article: PubMed Central - PubMed

Affiliation: Department of Theoretical and Applied Sciences, Università degli Studi dell'Insubria, Varese, Italy.

ABSTRACT
As widely recognized, tumor growth entails a close and complex cross-talk among cancer cells and the surrounding tumor microenvironment. We recently described the human RNASET2 gene as one key player of such microenvironmental cross-talk. Indeed, the protein encoded by this gene is an extracellular RNase which is able to control cancer growth in a non-cell autonomous mode by inducing a sustained recruitment of immune-competent cells belonging to the monocyte/macrophage lineage within a growing tumor mass. Here, we asked whether this oncosuppressor gene is sensitive to stress challenges and whether it can trigger cell-intrinsic processes as well. Indeed, RNASET2 expression levels were consistently found to increase following stress induction. Moreover, changes in RNASET2 expression levels turned out to affect several cancer-related parameters in vitro in an ovarian cancer cell line model. Of note, a remarkable rearrangement of the actin cytoskeleton organization, together with changes in cell adhesion and motility, emerged as putative mechanisms by which such cell-autonomous role could occur. Altogether, these biological features allow to put forward the hypothesis that the RNASET2 protein can act as a molecular barrier for limiting the damages and tissue remodeling events occurring during the earlier step of cell transformation.

No MeSH data available.


Related in: MedlinePlus