A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential

Abstract

Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.

High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma

“…Little is known about the role of SPARC in MPM. SPARC is expressed in MPM cell lines and patient tissue and blood samples [ 48 , 49 ]. In tissue samples, SPARC expression has been detected in stromal fibroblasts and MPM tumor cells [ 49 ].…”

Cell‐specific expression of runt‐related transcription factor 2 contributes to pulmonary fibrosis

“…RUNX2 has been predominantly studied in the context of bone, but has lately gained interest as a driver of different cancer types. RUNX2 is expressed by cancerous mesothelial cells, giving these cells the ability to transform into osteoblast‐like cells (32, 33). Interestingly, pleural mesothelial cell plasticity seems to play an important role in the process of pulmonary fibrosis in animal models as well as in IPF (34, 35).…”