Análise da modulação de parâmetros carcinogênicos de células de câncer de mama pelo tecido adiposo branco e marrom : o papel do inflamassoma NLRP3 neste processo

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Molecular, 2019.A influência do tecido adiposo na modulação de células tumorais tem sido altamente caracterizada. O tecido adiposo branco (WAT) e marrom (BAT) possuem a capacidade de mediar à inflamação através da secreção de citocinas inflamatórias, recrutando e polarizando células imunológicas para o microambiente, além de dar suporte energético às células tumorais, proporcionando um ambiente ideal para a progressão do tumor. No entanto, o papel do inflamassoma NLRP3 no tecido adiposo branco e marrom neste contexto é pouco conhecido. No presente trabalho, objetivamos caracterizar o papel dos componentes do inflamassoma NLRP3 no perfil lipídico do tecido adiposo branco e marrom, assim como caracterizar parâmetros celulares tumorais com ensaios de morte, viabilidade, ativação celular, além da caracterização da proteômica destas células sobre influência e tecidos adiposos. Nossos resultados mostraram que os produtos de secreção de BAT, especialmente na ausência de caspase-1/11, diminuíram a viabilidade, proliferação e ativação celular de câncer de mama em comparação com o WAT. Em adição, nossos dados sugerem que os produtos e secreção dos tecidos adiposos modulam de forma diferencial o recrutamento e polarização de células imunes como macrófagos e linfócitos. Além disso, a análise proteômica de células de câncer de mama revelou que os produtos de secreção de WAT modularam vias de proteínas de sobrevivência da linhagem celular tumoral. Análises da lipidômica de WAT e BAT mostraram que a ausência de caspase 1/11 modificou substancialmente o perfil global lipídico desses tecidos adiposos. Tomados em conjunto, nossos dados mostraram que WAT e BAT apresentaram funções opostas nos parâmetros carcinogênicos do câncer de mama. A ausência de caspase-1/11, mas não a proteína NLRP3, pode influenciar diretamente sua composição metabolômica e melhorar a capacidade do BAT de desencadear atividade antitumoral em células de câncer de mama.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) e Fundação de Apoio à Pesquisa do Distrito Federal (FAP/DF).The influence of adipose tissue on tumor cell modulation has been highly characterized. White (WAT) and brown (BAT) adipose tissues have the ability to mediate inflammation by secreting inflammatory cytokines, recruiting and polarizing immune cells into the microenvironment and providing energetic support to tumor cells, providing an ideal environment for the tumor progression. However, the role of the NLRP3 inflammasome in white and brown adipose tissue in this context is poorly understood. In the present work, we aimed to characterize the role of the NLRP3 inflammasome components in the lipid profile of white and brown adipose tissue, as well as to characterize tumor cell parameters with cell death analyses, viability, cell activation, and proteomic characterization of these cells on influence and tissues. adipose. Our results showed that BAT secretion products, especially in the absence of caspase-1/11, decreased breast cancer viability, proliferation, and cellular activation compared with WAT. In addition, our data showed that adipose tissue products and secretion differentially modulate the recruitment and polarization of immune cells such as macrophages and lymphocytes. In addition, proteomic analysis of breast cancer cells revealed that WAT secretion products modulated tumor cell line survival protein pathways. WAT and BAT lipid analyzes showed that the absence of caspase 1/11 substantially modified the overall lipid profile of these adipose tissues. Taken together, our data showed that WAT and BAT had opposite functions in the carcinogenic parameters of breast cancer. The absence of caspase-1/11, but not NLRP3 protein, can directly influence its metabolomic composition and improve BAT's ability to trigger antitumor activity in breast cancer cells

Adipocytes and macrophages interplay in the orchestration of tumor microenvironment : new implications in cancer progression

Inflammation has been known as one of the main keys to the establishment and progression of cancers. Chronic low-grade inflammation is also a strategic condition that underlies the causes and development of metabolic syndrome and obesity. Moreover, obesity has been largely related to poor prognosis of tumors by modulating tumor microenvironment with secretion of several inflammatory mediators by tumor-associated adipocytes (TAAs), which can modulate and recruit tumor-associated macrophages. Thus, the understanding of cellular and molecular mechanisms that underlay and link inflammation, obesity, and cancer is crucial to identify potential targets that interfere with this important route. Knowledge about the exact role of each component of the tumor microenvironment is not yet fully understood, but the new insights in literature highlight the essential role of adipocytes and macrophages interplay as key factor to determine the fate of cancer progression. In this review article, we focus on the functions of adipocytes and macrophages orchestrating cellular and molecular mechanisms that lead to inflammatory modulation in tumor microenvironment, which will be crucial to cancer establishment. We also emphasized the mechanisms by which the tumor promotes itself by recruiting and polarizing macrophages, discussing the role of adipocytes in this process. In addition, we discuss here the newest possible anticancer therapeutic treatments aiming to retard the development of the tumor based on what is known about cancer, adipocyte, and macrophage polarization

The impact of adipose tissue–derived miRNAs in metabolic syndrome, obesity, and cancer

Obesity is a multifactorial and complex condition that is characterized by abnormal and excessive white adipose tissue accumulation, which can lead to the development of metabolic diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, cardiovascular diseases, and several types of cancer. Obesity is characterized by excessive adipose tissue accumulation and associated with alterations in immunity, displaying a chronic low-grade inflammation profile. Adipose tissue is a dynamic and complex endocrine organ composed not only by adipocytes, but several immunological cells, which can secrete hormones, cytokines and many other factors capable of regulating metabolic homeostasis and several critical biological pathways. Remarkably, adipose tissue is a major source of circulating microRNAs (miRNAs), recently described as a novel form of adipokines. Several adipose tissue–derived miRNAs are deeply associated with adipocytes differentiation and have been identified with an essential role in obesity-associated inflammation, insulin resistance, and tumor microenvironment. During obesity, adipose tissue can completely change the profile of the secreted miRNAs, influencing circulating miRNAs and impacting the development of different pathological conditions, such as obesity, metabolic syndrome, and cancer. In this review, we discuss how miRNAs can act as epigenetic regulators affecting adipogenesis, adipocyte differentiation, lipid metabolism, browning of the white adipose tissue, glucose homeostasis, and insulin resistance, impacting deeply obesity and metabolic diseases. Moreover, we characterize how miRNAs can often act as oncogenic and tumor suppressor molecules, significantly modulating cancer establishment and progression. Furthermore, we highlight in this manuscript how adipose tissue–derived miRNAs can function as important new therapeutic targets

The impact of the adipose organ plasticity on inflammation and cancer progression

Obesity is characterized by chronic and low-grade systemic inflammation, an increase of adipose tissue, hypertrophy, and hyperplasia of adipocytes. Adipose tissues can be classified into white, brown, beige and pink adipose tissues, which display different regulatory, morphological and functional characteristics of their adipocyte and immune cells. Brown and white adipocytes can play a key role not only in the control of energy homeostasis, or through the balance between energy storage and expenditure, but also by the modulation of immune and inflammatory responses. Therefore, brown and white adipocytes can orchestrate important immunological crosstalk that may deeply impact the tumor microenvironment and be crucial for cancer establishment and progression. Recent works have indicated that white adipose tissues can undergo a process called browning, in which an inducible brown adipocyte develops. In this review, we depict the mechanisms involved in the differential role of brown, white and pink adipocytes, highlighting their structural, morphological, regulatory and functional characteristics and correlation with cancer predisposition, establishment, and progression. We also discuss the impact of the increased adiposity in the inflammatory and immunological modulation. Moreover, we focused on the plasticity of adipocytes, describing the molecules produced and secreted by those cells, the modulation of the signaling pathways involved in the browning phenomena of white adipose tissue and its impact on inflammation and cancer

Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression

Inflammation has been known as one of the main keys to the establishment and progression of cancers. Chronic low-grade inflammation is also a strategic condition that underlies the causes and development of metabolic syndrome and obesity. Moreover, obesity has been largely related to poor prognosis of tumors by modulating tumor microenvironment with secretion of several inflammatory mediators by tumor-associated adipocytes (TAAs), which can modulate and recruit tumor-associated macrophages. Thus, the understanding of cellular and molecular mechanisms that underlay and link inflammation, obesity, and cancer is crucial to identify potential targets that interfere with this important route. Knowledge about the exact role of each component of the tumor microenvironment is not yet fully understood, but the new insights in literature highlight the essential role of adipocytes and macrophages interplay as key factor to determine the fate of cancer progression. In this review article, we focus on the functions of adipocytes and macrophages orchestrating cellular and molecular mechanisms that lead to inflammatory modulation in tumor microenvironment, which will be crucial to cancer establishment. We also emphasized the mechanisms by which the tumor promotes itself by recruiting and polarizing macrophages, discussing the role of adipocytes in this process. In addition, we discuss here the newest possible anticancer therapeutic treatments aiming to retard the development of the tumor based on what is known about cancer, adipocyte, and macrophage polarization

Constant and decreasing periods of pineapple slices dried by infrared

The aim of the present study is to model the dehydration process of pineapple slices through infrared drying, as well as to determine the critical moisture content and the critical time to the dehydration process. Pineapple slices were cut 5.0 mm thick and 2.0 cm diameter, and dried by an infrared heating source equipped with a built-in scale at accuracy of 0.001 g, under the temperatures of 50, 60, 70, 80, 90 and 100 °C, until constant weight was reached. Mass variation readings were taken at 1.0 min intervals. The mathematical models met the experimental data. The modified model by Henderson and Pabis best represented the data about the drying process. The higher drying temperature led to higher critical moisture content (from 2.205 to 2.450 kgw kgdm -1) and to decreased critical time (18.00 to 5.99 min). The coefficient of effective diffusion increased due to temperature (2.848 x 10-15 to 1.439 x 10-14). The activation energy of the drying process was 33.632 kJ mol-1O objetivo do presente trabalho foi de modelar o processo de desidratação de fatias de abacaxi secadas por infravermelho, bem como determinar o teor de água crítico e o tempo crítico para o processo de desidratação. Fatias de abacaxi foram cortadas com 5,0 mm de largura e 2,0 cm de diâmetro e secadas com uma balança de infravermelho com precisão de 0,001 g, nas temperaturas de 50, 60, 70, 80, 90 e 100 ºC, até massa constante. Leituras da variação de massa foram obtidas em intervalos de 1,0 minuto. Modelos matemáticos foram ajustados aos dados experimentais. Henderson e Pabis Modificado foi o modelo que melhor representou os dados de secagem. Maiores temperaturas de secagem levaram a maiores valores de teor de água crítico (2,205 a 2,450 kgw kgdm -1) e decresceram o tempo crítico (18,00 a 5,99 min). O coeficiente de difusão efetivo aumentou com o incremento de temperatura (2,848 x 10-15 a 1,439 x 10-14) e a energia de ativação para o processo de secagem foi de 33,632 kJ mol-1.Conselho Nacional de Desenvolvimento Científico e Tecnológico/[]/CNPq/ BrazilUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro para Investigaciones en Granos y Semillas (CIGRAS

De queer a quare: uma aposta interseccional entre gênero, raça, etnia e classe

In this paper we attempt to problematize some of the limitations of queer theory, proposing a more unrestricted theoretical view, capable of establishing correlations between gender, race, ethnicity and class. In order to articulate such identity cleavages, we address the contributions of intersectional thinking and quare studies, an interventionist disciplinary project which amplifies the prototypical, analytical and epistemological dimensions of queer studies to incorporate key issues faced by lesbians, gays, bisexuals, and transgendered people of color. From the analysis of Blackberri’s song Beautiful Blackman (1989), Giovanni’s Room (1956), a novel by African-American writer James Baldwin, and the photographic text of Érica Malunguinho (2018), by Sérgio Fernandes, we depict the operational potential of such a new proposal, allowing clearer readings of quare identities, forcibly restrained by hegemonically instituted regimes.Este artigo visa problematizar alguns dos limites da analítica queer, propondo uma abordagem teórica mais alargada, capaz de estabelecer correlações entre gênero, raça, etnia e classe. A fim de articular essas clivagens identitárias, recorre-se às contribuições aportadas pelo pensamento interseccional e pelos estudos quare, projeto disciplinar intervencionista que amplifica os marcos das dimensões prototípica, analítica e epistemológica dos estudos queer com o propósito de incorporar questões enfrentadas por lésbicas, gays, bissexuais e transgêneros racializados. A partir da análise da canção Beautiful Blackman (1989), de Blackberri, do romance Giovanni’s Room (1956), do escritor afro-americano James Baldwin, e do texto fotográfico de Érica Malunguinho (2018) feito por Sérgio Fernandes, ilustra-se o potencial operante dessa nova proposta, arejando leituras mais apuradas das identidades quare, forçosamente refreadas por regimes hegemonicamente instituídos

Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells

The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed. DHA-treated breast cancer cells triggered increased caspase-1and gasdermin D activation, enhanced IL-1β secretion, translocated HMGB1 towards the cytoplasm, and membrane pore formation when compared to untreated cells, suggesting DHA induces pyroptosis programmed cell death in breast cancer cells. Moreover, caspase-1 inhibitor (YVAD) could protect breast cancer cells from DHA-induced pyroptotic cell death. In addition, membrane pore formation showed to be a lysosomal damage and ROS formation-depended event in breast cancer cells. DHA triggered pyroptosis cell death in MDA-MB-231by activating several pyroptosis markers in these cells. This is the first study that shows the effect of DHA triggering pyroptosis programmed cell death in breast cancer cells and it could improve the understanding of the omega-3 supplementation during breast cancer treatment