A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential

Our plain-English summary of A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential, by S.M. Lansley, B. Pedersen, C. Robinson, et al (Scientific Reports, 2016).

The study

• Authors: S.M. Lansley, B. Pedersen, C. Robinson, R.G. Searles, G. Sterrett, I. van Bruggen, R.A. Lake, S.E. Mutsaers, C.M. Prêle
• Journal: Scientific Reports
• Published: 2016;6:36349
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study asked whether mesothelioma cells can turn into bone-forming cells, which might explain why bone is sometimes found inside mesothelioma tumors. The authors examined a pleural mesothelioma biopsy from a 27-year-old woman with childhood asbestos exposure and found mineralized bone within the tumor. Cells in the bone area resembled the neighboring sarcomatoid tumor cells. Among tumors from 50 mice exposed to asbestos (fiber type not stated), 21% of MexTAg tumors and 27.2% of C57BL/6 wild-type tumors contained bone. Three human and three mouse mesothelioma cell lines were grown in bone-promoting (osteogenic) medium. One human line (NO36) and all three mouse lines deposited mineral, and all lines expressed bone-cell markers. Medium taken from NO36 cultures raised a bone-cell marker in another human line, LO68, but no mineral formed. In mice, the steroid dexamethasone did not increase bone formation, although AE5 tumors grew significantly more with it. The authors concluded that mesothelioma cells may contribute to the bone found in these tumors. They noted that other cell sources cannot be excluded.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: experiments on human and mouse mesothelioma cell lines, mouse tumor experiments, and microscopic examination of one human biopsy and archived mouse tumors
• Who was studied: Three human mesothelioma cell lines (NO36, LO68, JU77) from pleural effusions of patients, and three mouse mesothelioma cell lines (AE5, AB1, AE17). A biopsy from one 27-year-old woman with pleural malignant mesothelioma (PathWest, Perth, Western Australia). Archived asbestos-induced tumors from 50 mice (39 MexTAg and 11 C57BL/6 wild-type). Groups of 10 mice in the dexamethasone experiment.
• Exposure: Cells were grown in osteogenic medium for up to 21 days, and LO68 cells were also grown in medium conditioned by NO36 cells. Mice carrying AE5 or AB1 tumors received dexamethasone (0.5 mg/kg) or saline by intraperitoneal injection for 22 days. The mouse tumors and mouse cell lines were induced by asbestos; the fiber type is not stated. The patient had childhood asbestos exposure.
• Main results:
  • In the biopsy from the 27-year-old woman with childhood asbestos exposure, the tumor contained mineralized bone. Malignant-looking cells within the bone-like (osteoid) area resembled the adjacent sarcomatoid mesothelioma cells.
  • Of the 50 asbestos-exposed mice analyzed, 21% of MexTAg tumor samples and 27.2% of C57BL/6 wild-type tumor samples contained bone.
  • In osteogenic medium, the bone-cell marker alkaline phosphatase was detected in two of the three human cell lines, NO36 and LO68.
  • NO36 was the only human cell line to form mineralized nodules. All three mouse cell lines deposited mineral.
  • All cell lines expressed the bone-cell markers RUNX2, SPARC and SPP1 at day 0 and throughout the assay. RUNX2 rose by day 21 in the human lines, but among the mouse lines only AB1 showed elevated RUNX2, at day 15.
  • Medium conditioned by NO36 cells stimulated alkaline phosphatase in LO68 cells at levels similar to osteogenic medium. LO68 cells did not form mineralized nodules under any treatment.
  • In mice, dexamethasone did not enhance bone formation in AE5 or AB1 tumors.
  • AE5 tumors grew significantly more in dexamethasone-treated mice than in saline controls, and AE5 tumors in treated mice showed abundant collagen. AB1 tumors grew similarly in treated and control mice.
• The authors' conclusion: The authors concluded that the data show mesothelioma cells can differentiate into another mesenchymal cell type. They suggested that mesothelioma cells may contribute to the bone and other unusual (heterologous) elements seen in some mesothelioma tumors.
• Limitations the authors state:
  • The authors state that bone formation from other possible precursor cells within the tumor cannot be excluded.
  • Survival data were not available for the patient studied.
  • The authors state that the dexamethasone findings need further studies to confirm the response and its mechanism.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Mesothelial Cells, Osteopontin, Heterologous Elements.

Related studies

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• Stimulatory effects of the ionic products from Ca-Mg-Si bioceramics on both osteogenesis and angiogenesis in vitro — W. Zhai, H. Lu, et al. (2013)
• 3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts — Y. Xuan, Y. Guo, et al. (2024)
• miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma — M. Williams, M.B. Kirschner, et al. (2015)
• Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/fibrinogen/bredigite nanofibrous membranes and their integration with osteoblasts for guided bone regeneration — M. Kouhi, V. Jayarama Reddy, et al. (2019)
• Malignant pleural mesothelioma with osteoblastic heterologous elements: CT and MR imaging findings — G. Chave, L. Chalabreysse, et al. (2002)

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