Decoding the impact of the microenvironment and signaling pathways on the normal and tumoral adrenal gland

• Grant number: 21/04770-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2021
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Claudimara Ferini Pacicco Lotfi
• Grantee: Jean Lucas Kremer
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/02988-7 - Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney, AP.TEM
• Associated scholarship(s): 24/14165-6 - MODELING THE ADRENAL MICROENVIRONMENT IN 3D CULTURES: EFFECTS OF THE WNT PATHWAY ON EXTRACELLULAR MATRIX COMPOSITION AND FUNCTION, BE.EP.PD

Abstract

The extracellular matrix (MEC), defined as non-cellular component of the tissue, is responsible for structural integrity, cellular communication, transport of molecules and biochemically distinct, according to the tissue microenvironment. Biochemical changes in this composition promote different cell signaling in normal tissues and in pathological conditions, such as in the tumor, with impacts on tumor progression. The adrenal gland consists of a cortex, with three zones, glomerulosa, fasciculate and reticulate, and the medulla, surrounded by a fibrous capsule. The modulation of MEC in these different microenvironments can contribute to the development and physiological maintenance of these tissues. Therefore, unraveling the composition of ECM in the adrenal gland can help to better understand neoplastic processes. Therefore, we propose to decode the composition of the ECM, its interactions with different cellular components and the signaling pathways, under normal and neoplastic conditions of the adrenal gland. Our general objectives include: 1) decoding the composition of the ECM into normal, hyperplastic and tumoral adrenals; 2) analyze the crosstalk between MEC and the cellular components, by investigating the signaling pathways related to normal and tumor conditions; 3) investigate the impact of changes in MEC in vivo experimental models. These goals open possibility of new therapeutic strategies targeting ECM and the cell signaling pathways modulation promoted by adrenocortical tumors. We intend to identify the similarities and differences between the ECM composition of humans and experimental animals, to determine the main ECM components that impact the phenotype and cell signaling pathways of the normal and neoplastic gland, and that the experimental organotypic model obtained will guide new therapeutic strategies. (AU)