title: Adipocyte Secretome Increases Radioresistance of Malignant Melanocytes by Improving Cell Survival and Decreasing Oxidative Status.
abstract: Radiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenotype of these cells with a concomitant activation of the AKT signaling pathway. These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.
authors.affiliation: a   Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.|b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.|c   Ciências Químicas e Biomoléculas, CISA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Coelho
authors.affiliation: b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.|c   Ciências Químicas e Biomoléculas, CISA.
authors.forename: Liliana
authors.initials: L
authors.lastname: Silva
authors.affiliation: d   Radioterapia, Escola Superior de Tecnologia da Saúde do Porto, Instituto Politécnico do Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Faria
authors.affiliation: b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.|c   Ciências Químicas e Biomoléculas, CISA.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vieria
authors.affiliation: e   Serviço de Radioterapia, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Armanda
authors.initials: A
authors.lastname: Monteiro
authors.affiliation: e   Serviço de Radioterapia, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pinto
authors.affiliation: b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.|c   Ciências Químicas e Biomoléculas, CISA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Prudêncio
authors.affiliation: b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.|c   Ciências Químicas e Biomoléculas, CISA.
authors.forename: Rúben
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: a   Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.|b   Instituto de Inovação e Investigação em Saúde, University of Porto, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Soares
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D018384:Oxidative Stress / Q000528:radiation effects; D020543:Proteome / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*; D011879:Radiotherapy Dosage
chemical_list: D020543:Proteome