Patients with malignant mesothelioma (MM) often exhibit malignant pleural effusion (MPE), a condition in which cancer causes an abnormal amount of fluid to build up in the pleural space, the thin area between the layers that protect the lungs. In a recent study published in Respirology, researchers have shown that MPE has properties that enhance MM cell proliferation, migration, and resistance to chemotherapy drugs in culture.
The study, “Malignant pleural ﬂuid from mesothelioma has potent biological activities,” also shows that MPE can induce tumor growth in a mouse model of malignant mesothelioma, suggesting that MPE has an important role in the progression of the disease.
About 95 percent of mesothelioma patients have MPE, which commonly recurs during a patient’s disease course. Usually, researchers look at MPE as a byproduct of cancer that is associated with shortness of breath, focusing mainly on its physical effects and the best way to treat it.
As a result, the reason why mesotheliomas or other tumors that metastasize to the pleural space produce large quantities of pleural fluid remains unanswered. This is important as MPE, which has been shown to be abundant on growth factors and proteins that promote tumor proliferation, bathes the tumor cells in MM patients.
In this study, the researchers examined the biological capabilities of MPE fluid in promoting proliferation, migration, and chemoresistance of MM cells. They used pleural fluid samples collected from 151 patients with malignant pleural mesothelioma (MPM); 56 patients with metastatic pleural carcinoma; and 35 patients with benign pleural diseases, all randomly selected from the Autralian Mesothelioma Biobank cohort.
Yun Chor Gary Lee, from the University of Western Australia, and his team employed seven human masothelioma cell lines and three primary mesothelioma lines, and cultured them with the different MPE samples.
Results showed that pleural fluid from mesothelioma patients consistently stimulated cell proliferation 2.92-fold over control cells that were not cultured with MPE. Migration was also increased with MPE from mesothelioma patients 2.13-fold compared to controls.
Culturing MPM cell lines with MPE rendered them significantly more resistant to Platinol (cisplatin)/Alimta (pemetrexed) chemotherapy, researchers found. In the three cell lines tested, MPE decreased chemotherapy-induced cell death up to 3.9-fold.
In a mouse flank model of mesothelioma, infusing the tumor with MPE daily made it grow faster than when the tumors were infused with saline solutions.
“This study provides a proof-of-concept data on the potent and diverse biological roles of MPE fluid in mesothelioma,” the researchers wrote.
“We hypothesize that mesothelioma induces MPE accumulation to provide a culture media to which the tumor releases molecules providing a milieu that enhances tumor progression,” they wrote.