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

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.

RETRACTED: The effect of CELLFOODTM on radiotherapy or combined chemoradiotherapy: preclinical evidence

“…A mouse xenograft model of mesothelioma was created as previously described. 32 MSTO cell suspensions (2.5 × 10 6 ) in 0.2 ml complete medium were injected subcutaneously into the flank of CD1 nude mice ( n = 10/treatment group) and growth was measured twice weekly with callipers and calculated by the formula: 4/3 π × (large diameter) × (small diameter) 2 . In order to test the influence of doses on combined treatment, two different experimental designs were planned, as schematically summarized in Figure 1.…”

Identification of novel COX-2 / CYP19A1 axis involved in the mesothelioma pathogenesis opens new therapeutic opportunities

“…Further investigation was carried out on MPM lines by adding PGE2 or inhibiting it with rofecoxib, showing higher and lower presence of CYP19A1 in MPM cells, respectively, once again supporting the relationship between COX-2 and CYP19A1 that through a positive feedback loop sustains cell proliferation in MPM. On the other hand, E2 produced by CYP19A1 promotes MPM cell growth [ 35 , 36 ]. Thus reducing CYP19A1 expression via COX-2 and inhibiting CYP19A1 activity with an CYP19A1 inhibitor may be an effective strategy to block the interplay COX-2 - CYP19A1.…”

“…Exemestane, a CYP19A1 inhibitor, decreases E2 level and induces death of MPM cells. In MPM xenografts, the daily exemestane therapy results in the reduction of the tumor mass and plasmatic E2 levels [ 35 , 36 ]. These new findings, together with the known role of COX-2 in MPM, highlighted the possibility of a relationship between inflammation, COX-2 and CYP19A1 in malignant mesothelioma [ 37 ].…”

Lepidiumuridine A: A New Natural Uridine Derivative as a Phytoestrogen Isolated from the Seeds of Lepidium apetalum Willd.

“…There are two types of estrogen receptors, genomic nuclear ER α and ER β and the nongenomic GPR30 and potentially additional nongenomic receptors [ 26 ]. The receptors mediate the physiological and pathological impacts of estrogen, and western blot and in-cell western were utilized to examine ER α , Er β, and GPR30 expression in the uterus.…”