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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 protein re-localizes to P-bodies in response to chemically-induced hypoxiaA) SKOV3 cells were seeded on coverslips, treated with 200 μM CoCl2 for 24 hours and then processed for double IIF. No co-localization signal between RNASET2 and DCP-1A was detected in untreated SKOV3 cells, while a partial overlap (white arrowheads) was detected following treatment. Scale bar: 10 μm. B) A partial re-localization of RNASET2 protein to P-bodies (white arrowheads) was also detected in OVCAR3 cells following treatment. Confocal microscopy images. Scale bar: 25 μm. DCP-1A: de-capping enzyme 1A (PBs marker).
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Figure 4: RNASET2 protein re-localizes to P-bodies in response to chemically-induced hypoxiaA) SKOV3 cells were seeded on coverslips, treated with 200 μM CoCl2 for 24 hours and then processed for double IIF. No co-localization signal between RNASET2 and DCP-1A was detected in untreated SKOV3 cells, while a partial overlap (white arrowheads) was detected following treatment. Scale bar: 10 μm. B) A partial re-localization of RNASET2 protein to P-bodies (white arrowheads) was also detected in OVCAR3 cells following treatment. Confocal microscopy images. Scale bar: 25 μm. DCP-1A: de-capping enzyme 1A (PBs marker).

Mentions: In a previous work, we have shown that the intracellular RNASET2 protein pool is in part localized into Processing-bodies [17]. We thus re-evaluated these data in the context of the present results. As SKOV3 cells showed the highest increase in RNASET2 expression following stress induction (Figure 2B), we evaluated whether hypoxic stress in this cell line was associated with RNASET2 subcellular localization changes. As shown in Figure 4A, in the absence of stress no co-localization was observed between RNASET2 and the P-bodies marker DCP-1A. However, under hypoxic conditions, the RNASET2 protein showed a more punctuated cell pattern and a partial overlap with the DCP-1A signal, suggesting that a fraction of the RNASET2 intracellular pool is re-directed to P-bodies. The intracellular localization of RNASET2 in response to hypoxic stress was also evaluated in OVCAR3 cells, where a partial re-localization of RNASET2 to P-bodies was observed as well (Figure 4B). Of note, no localization changes for RNASET2 were detected with respect to lysosomes and stress granules under the same stress conditions (data not shown). These data suggest that the RNASET2 stress response role might in part be mediated by engagement of this protein to P-bodies.


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 protein re-localizes to P-bodies in response to chemically-induced hypoxiaA) SKOV3 cells were seeded on coverslips, treated with 200 μM CoCl2 for 24 hours and then processed for double IIF. No co-localization signal between RNASET2 and DCP-1A was detected in untreated SKOV3 cells, while a partial overlap (white arrowheads) was detected following treatment. Scale bar: 10 μm. B) A partial re-localization of RNASET2 protein to P-bodies (white arrowheads) was also detected in OVCAR3 cells following treatment. Confocal microscopy images. Scale bar: 25 μm. DCP-1A: de-capping enzyme 1A (PBs marker).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: RNASET2 protein re-localizes to P-bodies in response to chemically-induced hypoxiaA) SKOV3 cells were seeded on coverslips, treated with 200 μM CoCl2 for 24 hours and then processed for double IIF. No co-localization signal between RNASET2 and DCP-1A was detected in untreated SKOV3 cells, while a partial overlap (white arrowheads) was detected following treatment. Scale bar: 10 μm. B) A partial re-localization of RNASET2 protein to P-bodies (white arrowheads) was also detected in OVCAR3 cells following treatment. Confocal microscopy images. Scale bar: 25 μm. DCP-1A: de-capping enzyme 1A (PBs marker).
Mentions: In a previous work, we have shown that the intracellular RNASET2 protein pool is in part localized into Processing-bodies [17]. We thus re-evaluated these data in the context of the present results. As SKOV3 cells showed the highest increase in RNASET2 expression following stress induction (Figure 2B), we evaluated whether hypoxic stress in this cell line was associated with RNASET2 subcellular localization changes. As shown in Figure 4A, in the absence of stress no co-localization was observed between RNASET2 and the P-bodies marker DCP-1A. However, under hypoxic conditions, the RNASET2 protein showed a more punctuated cell pattern and a partial overlap with the DCP-1A signal, suggesting that a fraction of the RNASET2 intracellular pool is re-directed to P-bodies. The intracellular localization of RNASET2 in response to hypoxic stress was also evaluated in OVCAR3 cells, where a partial re-localization of RNASET2 to P-bodies was observed as well (Figure 4B). Of note, no localization changes for RNASET2 were detected with respect to lysosomes and stress granules under the same stress conditions (data not shown). These data suggest that the RNASET2 stress response role might in part be mediated by engagement of this protein to P-bodies.

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