LUCIANA NOGUEIRA DE SOUSA ANDRADE
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Secretory Autophagy Forges a Therapy Resistant Microenvironment in Melanoma(2022) BUSTOS, Silvina Odete; SANTOS, Nathalia Leal; CHAMMAS, Roger; ANDRADE, Luciana Nogueira de SousaSimple Summary Tumor microenvironment (TME) is a complex of many cell types and extracellular matrix that play an active role in regulating and sustaining melanoma tumor progression. In this context, the secretion of several molecules, by secretory autophagy or exosome release, stimulates the intercellular communication between the different components of the TME modulating tumor response. Here, we discuss the current awareness around the role of extracellular secretion in melanoma TME and also investigate the molecules related to these secretion pathways in melanoma progression using public databases. Melanoma is the most aggressive skin cancer characterized by high mutational burden and large heterogeneity. Cancer cells are surrounded by a complex environment, critical to tumor establishment and progression. Thus, tumor-associated stromal components can sustain tumor demands or impair cancer cell progression. One way to manage such processes is through the regulation of autophagy, both in stromal and tumor cells. Autophagy is a catabolic mechanism that provides nutrients and energy, and it eliminates damaged organelles by degradation and recycling of cellular elements. Besides this primary function, autophagy plays multiple roles in the tumor microenvironment capable of affecting cell fate. Evidence demonstrates the existence of novel branches in the autophagy system related to cytoplasmic constituent's secretion. Hence, autophagy-dependent secretion assembles a tangled network of signaling that potentially contributes to metabolism reprogramming, immune regulation, and tumor progression. Here, we summarize the current awareness regarding secretory autophagy and the intersection with exosome biogenesis and release in melanoma and their role in tumor resistance. In addition, we present and discuss data from public databases concerning autophagy and exosome-related genes as important mediators of melanoma behavior. Finally, we will present the main challenges in the field and strategies to translate most of the pre-clinical findings to clinical practice.
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells(2022) SAITO, Renata de Freitas; ANDRADE, Luciana Nogueira de Sousa; BUSTOS, Silvina Odete; CHAMMAS, RogerTo become resistant, cancer cells need to activate and maintain molecular defense mechanisms that depend on an energy trade-off between resistance and essential functions. Metabolic reprogramming has been shown to fuel cell growth and contribute to cancer drug resistance. Recently, changes in lipid metabolism have emerged as an important driver of resistance to anticancer agents. In this review, we highlight the role of choline metabolism with a focus on the phosphatidylcholine cycle in the regulation of resistance to therapy. We analyze the contribution of phosphatidylcholine and its metabolites to intracellular processes of cancer cells, both as the major cell membrane constituents and source of energy. We further extended our discussion about the role of phosphatidylcholine-derived lipid mediators in cellular communication between cancer and immune cells within the tumor microenvironment, as well as their pivotal role in the immune regulation of therapeutic failure. Changes in phosphatidylcholine metabolism are part of an adaptive program activated in response to stress conditions that contribute to cancer therapy resistance and open therapeutic opportunities for treating drug-resistant cancers.
- Tumor-Derived Extracellular Vesicles: Modulation of Cellular Functional Dynamics in Tumor Microenvironment and Its Clinical Implications(2021) SANTOS, Nathalia Leal; BUSTOS, Silvina Odete; BHATT, Darshak; CHAMMAS, Roger; ANDRADE, Luciana Nogueira de SousaCancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatment-resistant phenotype, and their potential as therapeutic targets for interventions such as the use of extracellular vesicle (EV) inhibitors to block their pro-tumoral activities. Some of the technical challenges for TEVs research and clinical use are also presented.
- Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles(2023) CARRASCO, Alexis German Murillo; OTAKE, Andreia Hanada; MACEDO-DA-SILVA, Janaina; SANTIAGO, Veronica Feijoli; PALMISANO, Giuseppe; ANDRADE, Luciana Nogueira de Sousa; CHAMMAS, RogerBreast cancer (BC) accounts for the highest incidence of tumor-related mortality among women worldwide, justifying the growing search for molecular tools for the early diagnosis and follow-up of BC patients under treatment. Circulating extracellular vesicles (EVs) are membranous nanocompartments produced by all human cells, including tumor cells. Since minimally invasive methods collect EVs, which represent reservoirs of signals for cell communication, these particles have attracted the interest of many researchers aiming to improve BC screening and treatment. Here, we analyzed the cargoes of BC-derived EVs, both proteins and nucleic acids, which yielded a comprehensive list of potential markers divided into four distinct categories, namely, (i) modulation of aggressiveness and growth; (ii) preparation of the pre-metastatic niche; (iii) epithelial-to-mesenchymal transition; and (iv) drug resistance phenotype, further classified according to their specificity and sensitivity as vesicular BC biomarkers. We discuss the therapeutic potential of and barriers to the clinical implementation of EV-based tests, including the heterogeneity of EVs and the available technologies for analyzing their content, to present a consistent, reproducible, and affordable set of markers for further evaluation.
- Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments(2016) CARDOSO, Ana Carolina Ferreira; ANDRADE, Luciana Nogueira de Sousa; BUSTOS, Silvina Odete; CHAMMAS, RogerGalectin-3 is a member of the beta-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1 alpha and NF-kappa B. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular galectin-3.
- Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy(2018) SILVA JUNIOR, Ildefonso Alves da; ANDRADE, Luciana Nogueira de Sousa; JANCAR, Sonia; CHAMMAS, RogerPlatelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.