Abstract
BackgroundMalignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.MethodsThe present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.ResultsLevels of CCL2 were significantly elevated in the serum of patients with advanced MPM.ConclusionsOur findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.
Highlights
Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity
We found that serum C motif chemokine ligand 2 (CCL2) levels were increased in mesothelioma patients and that this increase was dependent on advancing mesothelioma stage
The mean CCL2 level in the serum of the mesothelioma patients is significantly elevated compared to the Possibly Exposed group, and this increase is dependent on the stage of the disease
Summary
Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. A causal association between exposure to at least some types of asbestos and lung carcinomas and malignant pleural mesothelioma (MPM) has been long recognized [1], and in 2012 the WHO/International Agency for Research on Cancer (IARC, Lyon) classified all forms of asbestos (chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) as carcinogenic to humans [2]. In Japan, the number of patients that die of MPM is currently 1500 a year (Vital Statistics, Ministry of Health Labour and Welfare, Japan, 2015), and the incidence of MPM is predicted to remain relatively high in the coming years due to past exposure to asbestos
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