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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

Silencing of RNASET2 in OVCAR3 affects cell motilityA) A migration assay performed on pools of control vs. RNASET2-silenced OVCAR3 cells showed a significant increase in cell motility in RNASET2-silenced cells. B) A scratch test on the same cells also showed an increase in cell-motility in RNASET2-silenced cells when compared to control OVCAR3 cells at 48 hours after wounding. Asterisks indicate statistical significant values analyzed by Student's t-test. *** p<0,001.
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Figure 6: Silencing of RNASET2 in OVCAR3 affects cell motilityA) A migration assay performed on pools of control vs. RNASET2-silenced OVCAR3 cells showed a significant increase in cell motility in RNASET2-silenced cells. B) A scratch test on the same cells also showed an increase in cell-motility in RNASET2-silenced cells when compared to control OVCAR3 cells at 48 hours after wounding. Asterisks indicate statistical significant values analyzed by Student's t-test. *** p<0,001.

Mentions: We next investigated whether the observed RNASET2-mediated changes in actin cytoskeleton might also affect cell migration and invasion in vitro. To this end, control and RNASET2-silenced OVCAR3 cells were tested by a transmigration assay. Starved cells were seeded onto the transwell chambers and the migratory capability induced upon serum stimulation was monitored after 48 hr. RNASET2-silenced OVCAR3 cells showed 2-fold increased migration rate than the corresponding scrambled cells (Figure 6A). A scratch wound assay was also carried out as an independent test for migration, by measuring the area of the wounded surface at different time points. Again, RNASET2-silenced OVCAR3 cells turned out to show an increased cell-motility rate when compared to control cells (Figure 6B).


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)

Silencing of RNASET2 in OVCAR3 affects cell motilityA) A migration assay performed on pools of control vs. RNASET2-silenced OVCAR3 cells showed a significant increase in cell motility in RNASET2-silenced cells. B) A scratch test on the same cells also showed an increase in cell-motility in RNASET2-silenced cells when compared to control OVCAR3 cells at 48 hours after wounding. Asterisks indicate statistical significant values analyzed by Student's t-test. *** p<0,001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480721&req=5

Figure 6: Silencing of RNASET2 in OVCAR3 affects cell motilityA) A migration assay performed on pools of control vs. RNASET2-silenced OVCAR3 cells showed a significant increase in cell motility in RNASET2-silenced cells. B) A scratch test on the same cells also showed an increase in cell-motility in RNASET2-silenced cells when compared to control OVCAR3 cells at 48 hours after wounding. Asterisks indicate statistical significant values analyzed by Student's t-test. *** p<0,001.
Mentions: We next investigated whether the observed RNASET2-mediated changes in actin cytoskeleton might also affect cell migration and invasion in vitro. To this end, control and RNASET2-silenced OVCAR3 cells were tested by a transmigration assay. Starved cells were seeded onto the transwell chambers and the migratory capability induced upon serum stimulation was monitored after 48 hr. RNASET2-silenced OVCAR3 cells showed 2-fold increased migration rate than the corresponding scrambled cells (Figure 6A). A scratch wound assay was also carried out as an independent test for migration, by measuring the area of the wounded surface at different time points. Again, RNASET2-silenced OVCAR3 cells turned out to show an increased cell-motility rate when compared to control cells (Figure 6B).

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