Abstract

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 andsera of patients, and it has been widely debated whether MPM cells are able to produce HA bythemselves or through the release of growth factors stimulating other cells. Another key componentof the MPM microenvironment is C1q, which can act as a pro-tumorigenic factor favoring celladhesion, migration and proliferation. The aim of the current study was to prove that MPM primarycells 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 wellas an intracellular pool, mainly localized in the cytoplasmic and perinuclear region. After evaluatingHA synthase (HAS) enzymes’ basal expression in MPM primary cells, we found that C1q bound toHA was able to impinge upon HA homeostasis by upregulating HAS3 both at the mRNA and theprotein levels. High expression ofHAS3has been correlated with a shorter life expectancy in MPMby bioinformatical analysis. These data confirmed that C1q bound to HA may exert pro-tumorigenicactivity and identified HAS3 as a potential target in MPM.