Proangiogenic factor midkine is increased in melanoma patients with sleep apnea and induces tumor cell proliferation.

Autor: Cubillos-Zapata C; Grupo de Enfermedades Respiratorias, Servicio de Neumología, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain., Martínez-García MÁ; Respiratory Department, Hospital Universitario y Politécnico la Fe, Valencia, Spain., Díaz-García E; Grupo de Enfermedades Respiratorias, Servicio de Neumología, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain., Toledano V; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; TumorImmunology Laboratory IdiPAZ, Madrid, Spain.; Innate Immune Response Group, IdiPAZ, Madrid, Spain., Campos-Rodríguez F; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Respiratory Department, Hospital Universitario de Valme, IBIS, Seville, Spain., Sánchez-de-la-Torre M; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Group of Precision Medicine in Chronic Diseases, Hospital Universitari Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain., Nagore E; Dermatology Department, Instituto Valenciano de Oncología, Valencia, Spain., Martorell-Calatayud A; Dermatology Department, Hospital de Manises, Valencia, Spain., Hernández Blasco L; Respiratory Department, ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain.; Departamento Medicina Clinica, Universidad Miguel Hernandez, Elche, Spain., Pastor E; Respiratory Department, Hospital san Juan de Alicante, Alicante, Spain., Abad-Capa J; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Respiratory Department, Centro de investigacion Biomedica, Hospital Germans Trias i Pujol, Madrid, Spain., Montserrat JM; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Respiratory Department, Hospital Clinic- IDIBAPS, Barcelona, Spain., Cabriada-Nuño V; Respiratory Department, Hospital Universitario Cruces, Bilbao, Spain., Cano-Pumarega I; Respiratory Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Corral-Peñafiel J; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Respiratory Department, Hospital Universitario S. Pedro Alcántara, Cáceres, Spain., Arias E; Respiratory Department, Hospital 12 de Octubre, Madrid, Spain., Mediano O; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Respiratory Department, Hospital Universitario de Guadalajara, Guadalajara, Spain., Somoza-González M; Pneumology Department, Hospital Consorcio Terrassa, Barcelona, Spain., Dalmau-Arias J; Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Almendros I; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Farré R; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., López-Collazo E; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; TumorImmunology Laboratory IdiPAZ, Madrid, Spain.; Innate Immune Response Group, IdiPAZ, Madrid, Spain., Gozal D; Department of Child Health, University of Missouri School of Medicine, Columbia, MI, United States., García-Río F; Grupo de Enfermedades Respiratorias, Servicio de Neumología, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Dec; Vol. 34 (12), pp. 16179-16190. Date of Electronic Publication: 2020 Oct 15.
DOI: 10.1096/fj.202001247RR
Abstrakt: Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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