C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression
Increased hyaluronic acid (HA) production is often associated with cancer progression. In malignant pleural mesothelioma (MPM), HA is found at elevated levels in pleural effusions and sera of patients, and it has been widely debated whether MPM cells are able to produce HA by themselves or through t...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/3/416 |
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| author | Romana Vidergar Andrea Balduit Paola Zacchi Chiara Agostinis Alessandro Mangogna Beatrice Belmonte Micaela Grandolfo Francesco Salton Marco Biolo Fabrizio Zanconati Marco Confalonieri Roberta Bulla |
| author_facet | Romana Vidergar Andrea Balduit Paola Zacchi Chiara Agostinis Alessandro Mangogna Beatrice Belmonte Micaela Grandolfo Francesco Salton Marco Biolo Fabrizio Zanconati Marco Confalonieri Roberta Bulla |
| author_sort | Romana Vidergar |
| collection | DOAJ |
| description | Increased hyaluronic acid (HA) production is often associated with cancer progression. In malignant pleural mesothelioma (MPM), HA is found at elevated levels in pleural effusions and sera of patients, and it has been widely debated whether MPM cells are able to produce HA by themselves or through the release of growth factors stimulating other cells. Another key component of the MPM microenvironment is C1q, which can act as a pro-tumorigenic factor favoring cell adhesion, migration and proliferation. The aim of the current study was to prove that MPM primary cells are able to synthesize HA and to inquire the stimulus given by C1q–HA matrix to HA synthesis. We confirmed the presence of a HA coat and cable-like structures around MPM primary cells, as well as an intracellular pool, mainly localized in the cytoplasmic and perinuclear region. After evaluating HA synthase (HAS) enzymes’ basal expression in MPM primary cells, we found that C1q bound to HA was able to impinge upon HA homeostasis by upregulating HAS3 both at the mRNA and the protein levels. High expression of <i>HAS3</i> has been correlated with a shorter life expectancy in MPM by bioinformatical analysis. These data confirmed that C1q bound to HA may exert pro-tumorigenic activity and identified HAS3 as a potential target in MPM. |
| first_indexed | 2024-03-09T03:56:23Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:56:23Z |
| publishDate | 2021-01-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3f8e0d55ef094515abe28e019c6078a22023-12-03T14:20:16ZengMDPI AGCancers2072-66942021-01-0113341610.3390/cancers13030416C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 ExpressionRomana Vidergar0Andrea Balduit1Paola Zacchi2Chiara Agostinis3Alessandro Mangogna4Beatrice Belmonte5Micaela Grandolfo6Francesco Salton7Marco Biolo8Fabrizio Zanconati9Marco Confalonieri10Roberta Bulla11Department of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, ItalyTumor Immunology Unit, Department of Health Sciences, University of Palermo, 90133 Palermo, ItalyInternational School for Advanced Studies (SISSA), 34136 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, ItalyDepartment of Life Sciences, University of Trieste, 34127 Trieste, ItalyIncreased hyaluronic acid (HA) production is often associated with cancer progression. In malignant pleural mesothelioma (MPM), HA is found at elevated levels in pleural effusions and sera of patients, and it has been widely debated whether MPM cells are able to produce HA by themselves or through the release of growth factors stimulating other cells. Another key component of the MPM microenvironment is C1q, which can act as a pro-tumorigenic factor favoring cell adhesion, migration and proliferation. The aim of the current study was to prove that MPM primary cells are able to synthesize HA and to inquire the stimulus given by C1q–HA matrix to HA synthesis. We confirmed the presence of a HA coat and cable-like structures around MPM primary cells, as well as an intracellular pool, mainly localized in the cytoplasmic and perinuclear region. After evaluating HA synthase (HAS) enzymes’ basal expression in MPM primary cells, we found that C1q bound to HA was able to impinge upon HA homeostasis by upregulating HAS3 both at the mRNA and the protein levels. High expression of <i>HAS3</i> has been correlated with a shorter life expectancy in MPM by bioinformatical analysis. These data confirmed that C1q bound to HA may exert pro-tumorigenic activity and identified HAS3 as a potential target in MPM.https://www.mdpi.com/2072-6694/13/3/416malignant pleural mesotheliomacancerhyaluronic acidimmune systemcomplement systemC1q |
| spellingShingle | Romana Vidergar Andrea Balduit Paola Zacchi Chiara Agostinis Alessandro Mangogna Beatrice Belmonte Micaela Grandolfo Francesco Salton Marco Biolo Fabrizio Zanconati Marco Confalonieri Roberta Bulla C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression Cancers malignant pleural mesothelioma cancer hyaluronic acid immune system complement system C1q |
| title | C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression |
| title_full | C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression |
| title_fullStr | C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression |
| title_full_unstemmed | C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression |
| title_short | C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression |
| title_sort | c1q ha matrix regulates the local synthesis of hyaluronan in malignant pleural mesothelioma by modulating has3 expression |
| topic | malignant pleural mesothelioma cancer hyaluronic acid immune system complement system C1q |
| url | https://www.mdpi.com/2072-6694/13/3/416 |
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