000118639 001__ 118639
000118639 005__ 20231006143307.0
000118639 0247_ $$2doi$$a10.3390/cancers13194781
000118639 0248_ $$2sideral$$a127033
000118639 037__ $$aART-2021-127033
000118639 041__ $$aeng
000118639 100__ $$aKhalyfa A.
000118639 245__ $$aHeterogeneity of melanoma cell responses to sleep apnea-derived plasma exosomes and to intermittent hypoxia
000118639 260__ $$c2021
000118639 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118639 5203_ $$aObstructive sleep apnea (OSA) is associated with increased cutaneous melanoma incidence and adverse outcomes. Exosomes are secreted by most cells, and play a role in OSA-associated tumor progression and metastasis. We aimed to study the effects of plasma exosomes from OSA patients before and after adherent treatment with continuous positive airway pressure (CPAP) on melanoma cells lines, and also to identify exosomal miRNAs from melanoma cells exposed to intermittent hypoxia (IH) or normoxia. Plasma-derived exosomes were isolated from moderate-to-severe OSA patients before (V1) and after (V2) adherent CPAP treatment for one year. Exosomes were co-incubated with three3 different melanoma cell lines (CRL 1424; CRL 1619; CRL 1675) that are characterized by genotypes involving different mutations in BRAF, STK11, CDKN2A, and PTEN genes to assess the effect of exosomes on cell proliferation and migration, as well as on pAMK activity in the presence or absence of a chemical activator. Subsequently, CRL-1424 and CRL-1675 cells were exposed to intermittent hypoxia (IH) and normoxia, and exosomal miRNAs were identified followed by GO and KEG pathways and gene networks. The exosomes from these IH-exposed melanoma cells were also administered to THP1 macrophages to examine changes in M1 and M2 polarity markers. Plasma exosomes from V1 increased CRL-1424 melanoma cell proliferation and migration compared to V2, but not the other two cell lines. Exposure to CRL-1424 exosomes reduced pAMPK/tAMPK in V1 compared to V2, and treatment with AMPK activator reversed the effects. Unique exosomal miRNAs profiles were identified for CRL-1424 and CRL-1675 in IH compared to normoxia, with six miRNAs being regulated and several KEGG pathways were identified. Two M1 markers (CXCL10 and IL6) were significantly increased in monocytes when treated with exosomes from IH-exposed CRL-1424 and CRL-1625 cells. Our findings suggest that exosomes from untreated OSA patients increase CRL-1424 melanoma malignant properties, an effect that is not observed in two other melanoma cell lines. Exosomal cargo from CRL-1424 cells showed a unique miRNA signature compared to CRL-1675 cells after IH exposures, suggesting that melanoma cells are differentially susceptible to IH, even if they retain similar effects on immune cell polarity. It is postulated that mutations in STK-11 gene encoding for the serine/threonine kinase family that acts as a tumor suppressor may underlie susceptibility to IH-induced metabolic dysfunction, as illustrated by CRL-1424 cells. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
000118639 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118639 590__ $$a6.575$$b2021
000118639 591__ $$aONCOLOGY$$b60 / 245 = 0.245$$c2021$$dQ1$$eT1
000118639 592__ $$a1.349$$b2021
000118639 593__ $$aOncology$$c2021$$dQ1
000118639 593__ $$aCancer Research$$c2021$$dQ1
000118639 594__ $$a5.8$$b2021
000118639 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118639 700__ $$aTrzepizur W.
000118639 700__ $$aGileles-Hillel A.
000118639 700__ $$aQiao Z.
000118639 700__ $$0(orcid)0000-0002-5228-248X$$aSanz-Rubio D.
000118639 700__ $$0(orcid)0000-0001-9096-2294$$aMarin J.M.$$uUniversidad de Zaragoza
000118639 700__ $$aMartinez-Garcia M.A.
000118639 700__ $$aCampos-Rodriguez F.
000118639 700__ $$aAlmendros I.
000118639 700__ $$aFarre R.
000118639 700__ $$aSanchez-De-la-torre M.
000118639 700__ $$aGarcía-Río F.
000118639 700__ $$aGozal D.
000118639 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000118639 773__ $$g13, 19 (2021), 4781 [14 pp]$$pCancers$$tCancers$$x2072-6694
000118639 8564_ $$s3271063$$uhttps://zaguan.unizar.es/record/118639/files/texto_completo.pdf$$yVersión publicada
000118639 8564_ $$s2960839$$uhttps://zaguan.unizar.es/record/118639/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118639 909CO $$ooai:zaguan.unizar.es:118639$$particulos$$pdriver
000118639 951__ $$a2023-10-06-14:09:01
000118639 980__ $$aARTICLE