Vasculogenic mimicry in malignant mesothelioma: an experimental and immunohistochemical analysis

Our plain-English summary of Vasculogenic mimicry in malignant mesothelioma: an experimental and immunohistochemical analysis, by E. Pulford, A. Hocking, K. Griggs, et al (Pathology, 2016).

The study

• Authors: E. Pulford, A. Hocking, K. Griggs, J. McEvoy, C. Bonder, D.W. Henderson, S. Klebe
• Journal: Pathology
• Published: 2016;48(7):650-659
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Vasculogenic mimicry, the process in which cancer cells form angiomatoid structures independent of or in addition to host angiogenesis has been recorded in several otherwise non-endothelial malignant neoplasms. This study describes evidence of routine vascular mimicry by human mesothelioma cell lines in vitro, when the cell lines are cultured alone or co-cultured with human umbilical vascular endothelial cells, with the formation of angiomatoid tubular networks. Vasculogenic mimicry is also supported by immunohistochemical demonstration of human-specific anti-mitochondria antibody labelling of tumour-associated vasculature of human mesothelioma cells xenotransplanted into nude mice, and by evidence of vascular mimicry in some biopsy samples of human malignant mesotheliomas. These studies show mosaic interlacing of cells that co-label or label individually for immunohistochemical markers of endothelial and mesothelial differentiation. If vascular mimicry in mesothelioma can be characterised more fully, this may facilitate identification of more specific and targeted therapeutic approaches such as anti-angiogenesis in combination with chemotherapy and immunotherapy or other therapeutic approaches.

Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

In plain English

This was a laboratory study from Australia asking whether malignant mesothelioma cells can form their own blood-vessel-like channels, a process called vasculogenic mimicry. The authors grew five mesothelioma cell lines on a gel that lets three-dimensional structures form, without added growth factors. They also grew 12 samples of mesothelioma cells taken from pleural effusions (fluid around the lung) of eight patients. All five cell lines and all 12 patient samples formed tube-like networks within 6 hours. Normal mesothelial cells (the Met5a line and cells from benign fluid samples) did not. Mixed with human umbilical vein endothelial cells, the mesothelioma cells formed shared networks of both cell types. Human mesothelioma cells were also grown as tumours in nude mice. Some vessels at the tumour edge were lined by cells carrying a human-specific marker. In some of five human biopsy cases, tumour cells forming blood-containing channels stained for both an endothelial marker (CD31) and cytokeratins. The authors concluded that vasculogenic mimicry is a property of mesothelioma. They could not estimate how often it shows up in patient biopsies. The study did not measure asbestos exposure.

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 combining cell-culture experiments, an animal experiment (human mesothelioma cells grown as tumours in nude mice), and immunohistochemical study of five human biopsy cases
• Who was studied: Five mesothelioma cell lines (NCI-H226, NCI-H28, NCI-H2052, NCI-2452, MSTO-211H) and the normal mesothelial cell line Met5a. Twelve pleural effusion samples from eight patients (6 male, 2 female; 7 epithelioid and 1 sarcomatoid mesothelioma), plus four benign reactive effusions. Six BALB/C nude mice. Five human biopsy cases (two from 18 in-house mesotheliomas at Flinders Medical Centre over a 15-month interval in 2015 to 2016, three referrals), South Australia.
• Exposure: Asbestos exposure was not studied. The experiments examined mesothelioma cells and tissue. Asbestos appears only in the histories of two biopsy cases: a 63-year-old woman with past occupational exposure, and a 72-year-old woman with calcified pleural plaques whose husband had died of an asbestos-related disease. No fiber types are named.
• Main results:
  • All five mesothelioma cell lines formed tube-like structures after 6 hours on Matrigel without growth factors.
  • All 12 primary mesothelioma cell samples from pleural effusion fluids showed tube formation.
  • Mesothelial cells from benign reactive effusions and the normal Met5a cell line did not form these networks under the same conditions.
  • The tube-like structures formed in culture did not label for the endothelial marker CD31.
  • Primary mesothelioma cells cultured with human umbilical vein endothelial cells formed shared networks of both cell types, with no isolated islands of either.
  • In mouse tumours grown from the human NCI-H226 cell line, some vessels were lined by mouse cells. Cells lining blood-containing vessels at the tumour periphery labelled with a human-specific mitochondria antibody.
  • In some human biopsy samples, cytokeratin-positive tumour cells formed vascular channels containing red blood cells and co-labelled for CD31 and cytokeratins.
• The authors' conclusion: The authors concluded that vasculogenic mimicry is a property of malignant mesothelioma and that their in vitro findings point to it as a routine occurrence. They suggested that characterising it more fully might help identify more targeted treatment approaches.
• Limitations the authors state:
  • The authors could not estimate with any reasonable precision what proportion of mesotheliomas show evidence of vasculogenic mimicry in human biopsy tissue.
  • The authors stated that vasculogenic mimicry seems unrecognisable in most routine biopsy cases.
  • Only one of the primary effusion samples was of the sarcomatoid type.
  • The authors noted that a major diagnostic consideration in the illustrated biopsy cases is whether they are mesothelioma with vasculogenic mimicry or a vascular tumour such as angiosarcoma or epithelioid haemangioendothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Angiogenesis, Neoplasm, Mesothelioma, Biopsy, Chemotherapy, Immunotherapy.

Related studies

• Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non-small-cell lung carcinoma and malignant mesothelioma — R. Shen, J. Li, et al. (2016)
• Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2012)
• Angiogenic effect induced by mineral fibres — D. Carbonari, A. Campopiano, et al. (2011)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma — T.G. Johnson, K. Schelch, et al. (2018)
• Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies — P. Icard, X.D. Zhang, et al. (2012)

Browse more research in Pathology, or return to medical research.