Reduction of estradiol in human malignant pleural mesothelioma tissues may prevent tumour growth, as implied by in in-vivo and in-vitro models

Our plain-English summary of Reduction of estradiol in human malignant pleural mesothelioma tissues may prevent tumour growth, as implied by in in-vivo and in-vitro models, by B. Nuvoli, A. Sacconi, G. Cortese, et al (Oncotarget, 2016).

The study

• Authors: B. Nuvoli, A. Sacconi, G. Cortese, S. Germoni, B. Murer, R. Galati
• Journal: Oncotarget
• Published: 2016;7(30):47116-47126
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This study aimed to investigate intratumoural estradiol and estrogen-receptors (ERα, ERβ and GPR30) in malignant pleural mesothelioma (MPM) to understand their function. Here, we report that immunohistochemistry of estradiol showed cytoplasmatic staining in 95% of fifty-seven human MPM samples with a trend toward a negative correlation between estradiol levels and the median post-diagnosis survival time. ERβ was only focally positive in 5.3% of cases, GPR30 and ERα were negative in our cases of MPM. GPR30 was detected mainly in glycosylated form in MPM cells. Moreover, G15, a GPR30 antagonist, induced MPM cell death. Altogether, these data suggest that MPM cells produce E2 interact with glycosylated forms of GPR30, and this facilitates tumour growth. Estradiol was found in MPM cells and plasma from mice mesothelioma xenografts. Concurrent reduction in tumour mass and plasmatic estradiol levels were observed in the mice treated with exemestane, suggesting that the reduction of E2 levels inhibit MPM growth. Thus, it appears that agents reducing estradiol levels could be useful to MPM therapy.

In plain English

This laboratory study looked at the female hormone estradiol and its receptors in malignant pleural mesothelioma. It did not study asbestos exposure. The authors stained archived tumour samples from 57 patients at a hospital in Mestre-Venice, Italy, and normal pleura from control subjects. Estradiol staining was high in 14 of 57 tumours, intermediate in 28, low in 12 and negative in 3. Median survival was 27 months for patients whose tumours had no estradiol and about 14 months for the others. The authors called this a trend because very few tumours were estradiol-negative. The receptor ERβ was focally positive in 3 tumours, and ERα and GPR30 were not seen in the tumours. In cell lines, mesothelioma cells had more estradiol than normal mesothelial cells. Mice carried tumours grown from human mesothelioma cells. In mice treated with the drug exemestane, blood estradiol and tumour size at day 50 were lower than in untreated mice. The authors concluded that the findings possibly support further study of exemestane in mesothelioma. They noted that the tissue samples had been stored for years and their handling was unknown.

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: immunohistochemistry on archived human tumour tissue with survival comparison, cell-line experiments, and a mouse xenograft (animal) experiment
• Who was studied: Archived tissue from 57 patients with malignant pleural mesothelioma (48 male, 9 female, aged 45 to 80) plus normal control subjects, from the Regional Hospital of Mestre-Venice, Italy; also six cell lines and nude mice (10 per treatment group)
• Exposure: No asbestos exposure was studied. The study measured estradiol in tissue, cells and mouse blood, tested the GPR30 blocker G15 in cell lines, and treated mice with the aromatase inhibitor exemestane
• Main results:
  • Estradiol staining in the 57 mesothelioma samples: high in 14 (24.6%), intermediate in 28 (49.1%), low in 12 (21%), negative in 3 (5.3%)
  • ERβ was focally positive in only 3 mesothelioma cases
  • GPR30 was found in normal mesothelium but not in the mesothelioma cases; ERα was negative in normal and malignant cells
  • Median survival was 27 months for patients with estradiol-negative tumours and about 14 months for patients with low, intermediate or high estradiol (reported as P less than 0.05)
  • Two-year survival probability was 67% for patients without estradiol and 13% for those with low, intermediate or high estradiol
  • Normal mesothelial cells (Met5A) had significantly lower estradiol than the mesothelioma cell lines
  • In mice at day 50, exemestane-treated and control groups differed significantly in blood estradiol (P = 0.000509859) and tumour mass (P = 9.99382E-07)
  • The GPR30 blocker G15 caused cell death in two mesothelioma cell lines (MSTO, Ist-Mes1) but not in a third (NCI)
• The authors' conclusion: The authors concluded the findings are encouraging and possibly support further investigation of exemestane in the clinical mesothelioma setting
• Limitations the authors state:
  • Very few estradiol-negative samples, so the survival finding is described only as a trend
  • Tissue samples were stored from previous years and correct pre-analytical handling is not known
  • Cell lines were not authenticated by DNA fingerprinting
  • Estradiol could not be detected in cells after exemestane treatment, probably because of the test's sensitivity

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Immunohistochemistry, Mesothelioma.

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