Heat Shock Proteins Mediate Intercellular Communications within the Tumor Microenvironment through Extracellular Vesicles

Autor(es)

Saito, Renata F. ; Machado, Camila Maria Longo ; Lomba, Ana Luiza Oliveira ; Otake, Andreia Hanada ; Rangel, Maria Cristina

• Tipo de documento: Artigo Científico
• Fonte: APPLIED BIOSCIENCES; v. 3, n. 1, p. 14-pg., 2024-01-01.

Resumo

From an evolutive perspective, tumor cells endure successive turnover upon stress conditions and pressure to adapt to new environments. These cells use exceptional communication skills to share biological information to "survive upon every metabolic cost". The tumor microenvironment (TME) is a miscellaneous collection of cells, factors, and extracellular vesicles (EVs). EVs are small lipid bilayer-delimited particles derived from cells with sizes ranging from 100 to 1000 nm. Exosomes (<160 nm) are the minor subtype of EVs, originating from the endosomal pathways. The TME also contains "giant" vesicles, microvesicles (100-1000 nm, MV), originated from membrane blebbing. EVs can act as intercellular communication mediators, contributing to many biological processes, by carrying different biomolecules, such as proteins, lipids, nucleic acids, and metabolites. EV secretion can promote either tumor cell survival or manage their stress to death. Tumor-derived EVs transfer adaptative stress signaling to recipient cells, reprograming these cells. Heat shock proteins (HSP) are prominent stress response regulators, specifically carried by exosomes. HSP-loaded EVs reprogram tumor and TME cells to acquire mechanisms contributing to tumor progression and therapy resistance. The intercellular communication mediated by HSP-loaded EVs favors the escape of tumor cells from the endoplasmic reticulum stress, hypoxia, apoptosis, and anticancer therapies. Extracellular HSPs activate and deactivate the immune response, induce cell differentiation, change vascular homeostasis, and help to augment the pre-metastatic niche formation. Here we explore EVs' mechanisms of HSP transmission among TME cells and the relevance of these intercellular communications in resistance to therapy. (AU)

• Processo FAPESP: 19/07723-4 - Células tronco tumorais como alvo estratégico no tratamento do câncer de mama triplo-negativo
• Beneficiário: Maria Cristina Rodrigues Rangel
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 18/08107-2 - Células-tronco tumorais como alvo estratégico no tratamento do câncer de mama triplo-negativo
• Beneficiário: Maria Cristina Rodrigues Rangel
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/15445-1 - EMU concedido no processo 2018/08107-2: Estação de Hipóxia Whitley H35 com Filtragem HEPA
• Beneficiário: Maria Cristina Rodrigues Rangel
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários