Extracellular Vesicles Shedding Promotes Melanoma Growth in Response to Chemotherapy

Author(s)

de Sousa Andrade, Luciana Nogueira ^[1] ; Otake, Andreia Hanada ^[1] ; Braga Cardim, Silvia Guedes ^[1] ; da Silva, Felipe I. Lelis ^[1] ; Ikoma Sakamoto, Mariana Mari ^[1] ; Furuya, Tatiane Katsue ^[1] ; Uno, Miyuki ^[1] ; Pasini, Fatima Solange ^[1] ; Chammas, Roger ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Canc Estado Sao Paulo, Ctr Invest Translac On, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, OCT 9 2019.
• Web of Science Citations: 0

Abstract

Extracellular vesicles (EVs) are emerging as key players in intercellular communication. EVs can transfer biological macromolecules to recipient cells, modulating various physiological and pathological processes. It has been shown that tumor cells secrete large amounts of EVs that can be taken up by malignant and stromal cells, dictating tumor progression. In this study, we investigated whether EVs secreted by melanoma cells in response to chemotherapy modulate tumor response to alkylating drugs. Our findings showed that human and murine melanoma cells secrete more EVs after treatment with temozolomide and cisplatin. We observed that EVs shed by melanoma cells after temozolomide treatment modify macrophage phenotype by skewing macrophage activation towards the M2 phenotype through upregulation of M2-marker genes. Moreover, these EVs were able to favor melanoma re-growth in vivo, which was accompanied by an increase in Arginase 1 and IL10 gene expression levels by stromal cells and an increase in genes related to DNA repair, cell survival and stemness in tumor cells. Taken together, this study suggests that EVs shed by tumor cells in response to chemotherapy promote tumor repopulation and treatment failure through cellular reprogramming in melanoma cells. (AU)

• FAPESP's process: 18/01366-2 - 7th Annual International Society for Extracellular Vesicles (ISEV) Conference
• Grantee: Luciana Nogueira de Sousa Andrade
• Support Opportunities: Research Grants - Meeting - Abroad
• FAPESP's process: 14/03742-0 - Nanoparticles that bind to lipoprotein receptors in the treatment atherosclerosis, acute myocardial infarction, post-heart transplantation status, cancer and endometriosis
• Grantee: Raul Cavalcante Maranhao
• Support Opportunities: Research Projects - Thematic Grants