C1q–HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression

Cancers

卷:13

Paola Zacchi¹  Andrea Balduit¹  Romana Vidergar¹  Roberta Bulla¹  Fabrizio Zanconati²  Francesco Salton²  Marco Biolo²  Marco Confalonieri²  Alessandro Mangogna³  Chiara Agostinis³  Micaela Grandolfo⁴  Beatrice Belmonte⁵ 

[1] Department of Life Sciences, University of Trieste, 34127 Trieste, Italy;

[2] Department of Medical, Surgical and Health Science, University of Trieste, 34129 Trieste, Italy;

[3] Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34134 Trieste, Italy;

[4] International School for Advanced Studies (SISSA), 34136 Trieste, Italy;

[5] Tumor Immunology Unit, Department of Health Sciences, University of Palermo, 90133 Palermo, Italy;

关键词: malignant pleural mesothelioma;    cancer;    hyaluronic acid;    immune system;    complement system;    C1q;   

DOI  :  10.3390/cancers13030416

来源: DOAJ

【 摘 要 】

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 HAS3 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.

【 授权许可】

Unknown