Human renal angiomyolipoma cells of male and female origin can migrate and are influenced by microenvironmental factors

Abstract

BackgroundImproving the knowledge of angiomyolipoma physiopathology might help in refining its pharmacological treatment. We investigated if angiomyolipoma cells have migratory properties, how their growth and motility can be influenced by the hormonal milieu, and if this can be related to a specific gender.MethodsPrimary cells were isolated from angiomyolipomas surgically resected for therapeutical reasons in a female and in a male patient. The genetic control demonstrated no TSC2 deletion. Bi- (wound healing) and three-dimensional (transwell assay) migration were analyzed in vitro in basal conditions and under the influence of 17- β-estradiol and SDF-1α.ResultsTreatment up to 72 hours with 17-β-estradiol (0.1–100 nM), tamoxifen (0.2–20 μM) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1α and 17-β-estradiol treatment induce a significant motility increase (both bi- and three-dimensional) which becomes evident already after 2 hours of incubation. Angiomyolipoma cells express mRNA coding for SDF-1α and 17-β-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9.ConclusionAngiomyolipoma cells behave similarly, despite their different source. Primary angiomyolipoma cells migrate in response to hormonal milieu and soluble factors, and produce active metalloproteases, both aspects being consistent with the theory claiming they can migrate to the lungs (and/or other organs) and colonizing them. No main feature, among the aspects we analyzed, seems to be referable to the gender of origin.

Tuberous Sclerosis Complex cell‐derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers

“…We found altered expression of 42 tumour‐associated proteins in TSC2 ‐ cells relative to TSC2 + cells (Figure 2a ). Some of the proteins with elevated expression in TSC2 ‐ cells have previously been linked to mTORC1‐driven tumours in TSC, including HIF‐1α, MMPs, VE‐cadherin, IL‐6 and VEGF (Bertolini et al., 2018 ; Dodd et al., 2015 ; Lee et al., 2010 ; Shu et al., 2010 ; Wang et al., 2021 ; Young et al., 2013 ). 29 tumour‐associated proteins were found to have altered expression in EVs from TSC2 ‐ cells compared to the EVs from TSC2 + controls.…”

Rapamycin-upregulated miR-29b promotes mTORC1-hyperactive cell growth in TSC2-deficient cells by downregulating tumor suppressor retinoic acid receptor β (RARβ)

“…This miR-29b/RARβ/ING4 axis could be relevant to pulmonary LAM, which is believed to result from the metastasis of benign smooth muscle-like cells to the lung. These cells can lead to cystic lung destruction, oxygen dependency, and death [49–51]. Thus, restoration of RARβ2 and ING4 by inhibiting miR-29b could be beneficial in reducing the migratory and invasive potential of LAM cells.…”

Epicatechin Gallate Protects HBMVECs from Ischemia/Reperfusion Injury through Ameliorating Apoptosis and Autophagy and Promoting Neovascularization

“…To measure cell migration ability, transwell migration assay was performed as previously reported [ 27 , 28 ]. Briefly, 0.5 × 10 4 HBMVECs suspended in 200 μ L of culture medium with/without drugs were seeded in the upper chamber of transwell (BD) followed by OGD/R and then placed in 24-well plates, and the lower chamber was filled with fresh culture medium.…”