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
2 resultados
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- NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients(2019) JANDREY, Elisa H. F.; MOURA, Ricardo P.; ANDRADE, Luciana N. S.; MACHADO, Camila L.; CAMPESATO, Luiz Felipe; LEITE, Katia Ramos M.; INOUE, Lilian T.; ASPRINO, Paula F.; SILVA, Ana Paula M. da; BARROS, Alfredo Carlos S. D. de; CARVALHO, Andre; LIMA, Vladmir C. de; CARRARO, Dirce M.; BRENTANI, Helena P.; CUNHA, Isabela W. da; SOARES, Fernando A.; PARMIGIANI, Raphael B.; CHAMMAS, Roger; CAMARGO, Anamaria A.; COSTA, Erico T.The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20-30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response. Here, we present N-Myc downstream-regulated gene 4 (NDRG4) epigenetic silencing as a mechanistic biomarker of metastasis in ductal invasive breast tumors. While aberrant NDRG4 DNA hypermethylation is significantly associated with the development of metastatic disease, downregulation of NDRG4 transcription and protein expression is functionally associated with enhanced lymph node adhesion and cell mobility. Here, we show that epigenetic silencing of NDRG4 modulates integrin signaling by assembling beta 1-integrins into large punctate clusters at the leading edge of tumor cells to promote an ""adhesive switch,"" decreasing cell adhesion to fibronectin and increasing cell adhesion and migration towards vitronectin, an important component of human lymph nodes. Taken together, our functional and clinical observations suggest that NDRG4 is a potential mechanistic biomarker in breast cancer that is functionally associated with metastatic disease.
- Extracellular Vesicles Shedding Promotes Melanoma Growth in Response to Chemotherapy(2019) ANDRADE, Luciana Nogueira de Sousa; OTAKE, Andreia Hanada; CARDIM, Silvia Guedes Braga; SILVA, Felipe I. Lelis da; SAKAMOTO, Mariana Mari Ikoma; FURUYA, Tatiane Katsue; UNO, Miyuki; PASINI, Fatima Solange; CHAMMAS, RogerExtracellular vesicles (EVs) are emerging as key players in intercellular communication. EVs can transfer biological macromolecules to recipient cells, modulating various physiological and pathological processes. It has been shown that tumor cells secrete large amounts of EVs that can be taken up by malignant and stromal cells, dictating tumor progression. In this study, we investigated whether EVs secreted by melanoma cells in response to chemotherapy modulate tumor response to alkylating drugs. Our findings showed that human and murine melanoma cells secrete more EVs after treatment with temozolomide and cisplatin. We observed that EVs shed by melanoma cells after temozolomide treatment modify macrophage phenotype by skewing macrophage activation towards the M2 phenotype through upregulation of M2-marker genes. Moreover, these EVs were able to favor melanoma re-growth in vivo, which was accompanied by an increase in Arginase 1 and IL10 gene expression levels by stromal cells and an increase in genes related to DNA repair, cell survival and stemness in tumor cells. Taken together, this study suggests that EVs shed by tumor cells in response to chemotherapy promote tumor repopulation and treatment failure through cellular reprogramming in melanoma cells.