Reduction of estradiol in human malignant pleural mesothelioma tissues may prevent tumour growth, as implied by in in-vivo and in-vitro models.
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.
Preclinical Models and New Therapeutic Agent Unit, Regina Elena National Cancer Institute, Rome, Italy.
Barbara
B
Nuvoli
Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Rome, Italy.
Andrea
A
Sacconi
SAFU Unit, Regina Elena National Cancer Institute, Rome, Italy.
Giancarlo
G
Cortese
SAFU Unit, Regina Elena National Cancer Institute, Rome, Italy.
Sabrina
S
Germoni
Department of Anatomic Pathology, Mestre Hospital, Venezia, Italy.
Bruno
B
Murer
Preclinical Models and New Therapeutic Agent Unit, Regina Elena National Cancer Institute, Rome, Italy.
Rossella
R
Galati
D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000473:pathology
D004958:Estradiol
GPR30; estradiol; estrogen receptor α; estrogen receptor β; mesothelioma