Heparanase regulates EMT and cancer stem cell properties in prostate tumors
Prostate cancer displays a certain phenotypic plasticity that allows for the transition of cells from the epithelial to the mesenchymal state. This process, known as epithelial–mesenchymal transition (EMT), is one of the factors that give the tumor cells greater invasive and migratory capacity with...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.918419/full |
| _version_ | 1818161925016518656 |
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| author | Valentina Masola Marco Franchi Gianluigi Zaza Francesca Mansa Atsina Giovanni Gambaro Maurizio Onisto |
| author_facet | Valentina Masola Marco Franchi Gianluigi Zaza Francesca Mansa Atsina Giovanni Gambaro Maurizio Onisto |
| author_sort | Valentina Masola |
| collection | DOAJ |
| description | Prostate cancer displays a certain phenotypic plasticity that allows for the transition of cells from the epithelial to the mesenchymal state. This process, known as epithelial–mesenchymal transition (EMT), is one of the factors that give the tumor cells greater invasive and migratory capacity with subsequent formation of metastases. In addition, many cancers, including prostate cancer, are derived from a cell population that shows the properties of stem cells. These cells, called cancer stem cells (CSCs) or tumor-initiating cells, not only initiate the tumor process and growth but are also able to mediate metastasis and drug resistance. However, the impact of EMT and CSCs in prostate cancer progression and patient survival is still far from fully understood. Heparanase (HPSE), the sole mammalian endoglycosidase capable of degrading heparan sulfate (HS), is also involved in prostate cancer progression. We had previously proved that HPSE regulates EMT in non-cancerous pathologies. Two prostate cancer cell lines (DU145 and PC3) were silenced and overexpressed for HPSE. Expression of EMT and stemness markers was evaluated. Results showed that the expression of several EMT markers are modified by HPSE expression in both the prostate cancer cell lines analyzed. In the same way, the stemness markers and features are also modulated by HPSE expression. Taken together, the present findings seem to prove a new mechanism of action of HPSE in sustaining prostate cancer growth and diffusion. As for other tumors, these results highlight the importance of HPSE as a potential pharmacological target in prostate cancer treatment. |
| first_indexed | 2024-12-11T16:25:30Z |
| format | Article |
| id | doaj.art-70a4608fcd794b358b7e240bcf57cd4c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T16:25:30Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-70a4608fcd794b358b7e240bcf57cd4c2022-12-22T00:58:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.918419918419Heparanase regulates EMT and cancer stem cell properties in prostate tumorsValentina Masola0Marco Franchi1Gianluigi Zaza2Francesca Mansa Atsina3Giovanni Gambaro4Maurizio Onisto5Department of Biomedical Sciences, University of Padova, Padova, ItalyDepartment of Life Quality Sciences, University of Bologna, Rimini, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, ItalyUniversity Hospital of Verona, Verona, ItalyRenal Unit, Department of Medicine, University Hospital of Verona, Verona, ItalyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyProstate cancer displays a certain phenotypic plasticity that allows for the transition of cells from the epithelial to the mesenchymal state. This process, known as epithelial–mesenchymal transition (EMT), is one of the factors that give the tumor cells greater invasive and migratory capacity with subsequent formation of metastases. In addition, many cancers, including prostate cancer, are derived from a cell population that shows the properties of stem cells. These cells, called cancer stem cells (CSCs) or tumor-initiating cells, not only initiate the tumor process and growth but are also able to mediate metastasis and drug resistance. However, the impact of EMT and CSCs in prostate cancer progression and patient survival is still far from fully understood. Heparanase (HPSE), the sole mammalian endoglycosidase capable of degrading heparan sulfate (HS), is also involved in prostate cancer progression. We had previously proved that HPSE regulates EMT in non-cancerous pathologies. Two prostate cancer cell lines (DU145 and PC3) were silenced and overexpressed for HPSE. Expression of EMT and stemness markers was evaluated. Results showed that the expression of several EMT markers are modified by HPSE expression in both the prostate cancer cell lines analyzed. In the same way, the stemness markers and features are also modulated by HPSE expression. Taken together, the present findings seem to prove a new mechanism of action of HPSE in sustaining prostate cancer growth and diffusion. As for other tumors, these results highlight the importance of HPSE as a potential pharmacological target in prostate cancer treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.918419/fullprostate cancerheparanaseepithelial to mesenchymal transitioncancer stem cellsin vitro |
| spellingShingle | Valentina Masola Marco Franchi Gianluigi Zaza Francesca Mansa Atsina Giovanni Gambaro Maurizio Onisto Heparanase regulates EMT and cancer stem cell properties in prostate tumors Frontiers in Oncology prostate cancer heparanase epithelial to mesenchymal transition cancer stem cells in vitro |
| title | Heparanase regulates EMT and cancer stem cell properties in prostate tumors |
| title_full | Heparanase regulates EMT and cancer stem cell properties in prostate tumors |
| title_fullStr | Heparanase regulates EMT and cancer stem cell properties in prostate tumors |
| title_full_unstemmed | Heparanase regulates EMT and cancer stem cell properties in prostate tumors |
| title_short | Heparanase regulates EMT and cancer stem cell properties in prostate tumors |
| title_sort | heparanase regulates emt and cancer stem cell properties in prostate tumors |
| topic | prostate cancer heparanase epithelial to mesenchymal transition cancer stem cells in vitro |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.918419/full |
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