Investigating the role of exosomes derived from chemotherapy resistant lymphoma cells as mediators of cellular plasticity

• Grant number: 19/09510-8
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): June 11, 2019
• Effective date (End): October 12, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Heidge Fukumasu
• Grantee: Taismara Kustro Garnica
• Supervisor: David John Argyle
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Research place: University of Edinburgh, Scotland
• Associated to the scholarship: 17/15406-3 - Extracellular vesicles as potencial predictive marker in canine multicentric lymphoma, BP.MS

Abstract

Canine lymphomas are a diverse group of cancers and are among the most common cancers diagnosed in dogs. There are over 30 described types of canine lymphoma, and these cancers vary tremendously in their behavior. Lymphomas may affect any organ in the body, but most commonly originate in lymph nodes, before spreading to other organs,such as the spleen, liver and bone marrow. Multicentric lymphoma is the most common type of lymphoma in the dog, and the most effective therapy is a combination of chemotherapy drugs given over several weeks. However, there are high rates of relapse and no accurate diagnostic test to predict therapeutic response. Exosomes are nanovesicles (containing an assortment of cytokines, growth factors, proteins, lipids, and microRNAs) secreted by cells into the extracellular milieu where they can be taken up by neighbouring cells, or travel to distant tissues, and mediate various biological processes: exosomes have been heralded as key mediators of intercellular communication. In human breast cancer, exosomal transfer of material, such as miRNA, has been implicated in the acquisition of chemo-resistance and enhanced oncogenicity. Studies have shown that hypoxic conditions significantly increase the number of exosomes shed from human breast cancer cells and dramatically enhance breast tumour metastasis in vivo. Limited research into the role of exosomes in the cancer of companion animals has been conducted. We propose that chemo-resistant lymphoma cells secrete exosomes that can drive phenotypic switching of cancer cell populations and enhance chemo-resistant phenotype. (AU)