Role of extracellular vesicles in the progression of renal cell carcinoma

• Grant number: 23/09378-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: December 01, 2023
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Aline Seiko Carvalho Tahyra
• Supervisor: Guido Jenster
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Erasmus University Rotterdam (EUR), Netherlands
• Associated to the scholarship: 21/12951-6 - Role of extracellular vesicles in Renal Cell Carcinoma progression, BP.DD

Abstract

Cancer represents a set of malignant neoplastic diseases and is a leading cause of death worldwide. Kidney cancer represents 4.6% of the total number of cancer diagnoses in 2020, according to WHO. Despite the low percentage, it represents approximately 430,000 cases, which 90% correspond to Renal Cell Carcinoma (RCC). This neoplasm originates in the tubular epithelial cells of the nephron, the kidney functional unit. The 5-year relative survival is directly related to the stage of the tumor at diagnosis, with a drastic drop in the rate when identified in the metastatic stage. Nowadays we are experiencing the "Golden Age" in relation to the state of the art in renal cancer research, but to overcome the alarming epidemiological data, it is still necessary to deepen the knowledge of this neoplasm biology. Regarding cell biology, extracellular vesicles (EVs) have emerged as a new paradigm of communication in physiological and pathological states. Despite evidence of their role in several tumors, little is known about EVs in the context of RCC. Thus, this project aims to deep into the EVs contribution in hypoxia and metastasis. For this study, the 3D technique culture is being implemented, allowing the mimicry of tumor architecture with greater similarity than the 2D culture aiming. More specifically, through 3D cultures, we propose to do the following aiming: (i) to correlate HIF-1± expression in EVs with the metabolic adaptation seen in RCC tumorigenesis; (ii) to evaluate the expression of CXCR4 and vimentin metastasis markers in EVs and correlate with the migratory-invasive capacity of RCC tumor cell; and (iii) to identify the proteome profile from RCC-derived EVs content. Thus, it is expected to bring to light new perspectives on the EVs contribution to the RCC development, seeking to open doors for further studies and clinical applications such as the investigation of biomarkers and therapeutic targets. (AU)