Biology subjects

Ortiz-de-Solorzano, C.

Publications and source records attributed to Ortiz-de-Solorzano, C..

2 recordsLinked to original sources

bioRxiv2025

Quantitative evaluation of the role of the microenvironment in the phenotype, metabolism, and drug resistance of PDAC tumor organoids

Tumor organoids are powerful tools to study cancer. However, the clinical translation of organoid-based studies depends on how closely the organoid scaffolding material recapitulates the tumor extracellular matrix (ECM). We present a quantitative analysis of the effect of scaffold composition on the phenotype, tissue remodeling, metabolism, and drug resistance of pancreatic ductal adenocarcinoma (PDAC) organoids. We grew PDAC organoids within hydrogels made of Matrigel, collagen-I, or a mixture of collagen-I and Matrigel. Our results show that 1) PDAC organoids grown in Matrigel-only are phenotypically and metabolically similar to low-physiological two-dimensional PDAC cultures; 2) collagen-containing hydrogels, and especially so those grown in hydrogels of mixed collagen-Matrigel composition, accurately reproduce invasive tumors that underwent epithelial-to-mesenchymal transition (EMT) regarding phenotype, tissue remodeling, metabolic activity, and drug resistance. In summary, our work illustrates the importance of three-dimensional (3D) matrix composition for PDAC growth and postulates that organoids grown in collagen-Matrigel hydrogels are the most adequate for studying the biology of invasive PDAC tumors.

bioengineering↗

bioRxiv2022

GLUT1 ablation in astrocytes paradoxically improves central and peripheral glucose metabolism via enhanced insulin-stimulated ATP release

Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e. GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 ablation (GLUT11'GFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Importantly, GLUT11'GFAP mice did not present cognitive alterations. Mechanistically, we observed that GLUT1-ablated astrocytes exhibited increased insulin receptor-dependent ATP release, and both astrocyte insulin signalling and brain purinergic signalling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its ablation triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis and cognitive function.

neuroscience↗