Journal
PLOS ONE
Volume 13, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0199371
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Funding
- Universita degli Studi di Torino
- Universita degli Studi del Piemonte Orientale
- Compagnia di San Paolo
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Background Improving 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. Methods Primary 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-beta-estradiol and SDF-1 alpha. Results Treatment up to 72 hours with 17-beta-estradiol (0.1 +/- 100 nM), tamoxifen (0.2 +/- 20 mu M) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1 alpha and 17-beta-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-1 alpha and 17-beta-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9. Conclusion Angiomyolipoma 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.
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