Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells

Abstract

Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.

Occupational exposure to carcinogens: Benzene, pesticides and fibers

“…Therefore, it was hypothesized that the detection of high plasma levels of fibulin-3, observed in street cleaners from the Biancavilla area, may be due to FE exposure. However, volcanic particulate exposure did not affect fibulin-3 expression (126,127). …”

“…Intriguingly, it was demonstrated that plasma levels of fibulin-3 were significantly lower in the group of workers exposed to asbestos fibers compared to those exposed to FE (126), suggesting that asbestos disposal workers properly used the personal protective equipment according to the current regulations. By contrast, other workers, such as street cleaners exhibited high levels of fibulin-3, indicating that these workers should be better equipped in order to prevent injury caused by FE found in dust deposited on the ground (126).…”

“…Recently, it has been shown that in subjects exposed to such fibers, tumor expansion is associated with the activation of fibulin-3 (126). High levels of fibulin-3 were detected in plasma samples of street cleaners from Biancavilla (Sicily), which are at high risk of FE exposure (126). …”

“…By contrast, other workers, such as street cleaners exhibited high levels of fibulin-3, indicating that these workers should be better equipped in order to prevent injury caused by FE found in dust deposited on the ground (126). …”

“…Accordingly, our most recent in vitro study indicated that fibulin-3 was overexpressed in mesothelial cells following treatment with FE and not following treatment with other particulates at both the transcript and protein level (126). Therefore, it was hypothesized that the detection of high plasma levels of fibulin-3, observed in street cleaners from the Biancavilla area, may be due to FE exposure.…”