Biology subjects

Costa, E. T.

Publications and source records attributed to Costa, E. T..

2 recordsLinked to original sources

bioRxiv2022

PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state.

Extracellular vesicles (EV) are comprised of vesicles budding from cell membranes and smaller intracellular vesicles shed by cells. EV play a role in remodeling the tumor microenvironment (TME) and support tumor progression. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with a carboxypeptidase function, frequently associated with poor clinical prognosis in prostate cancer (PCa). We previously identified an oncogenic PSMA signaling function in prostate cancer. Others demonstrated that EV isolated from the plasma of patients with high-grade PCa carry PSMA, but so far no pathophysiological effect has been associated with PSMA-bearing EV. Here we demonstrate that EV from PCa cells are able to transfer PSMA and its functionality to cells in the TME. The consequence of that EV-mediated PSMA transfer is an acute to long-term increased secretion of vascular endothelial growth factor-A (VEGF-A), angiogenin, pro-angiogenic and pro-lymphangiogenic mediators and increased 4E binding protein 1 (4EBP-1) phosphorylation in tumors. We compare EV from PCa cells with or without PSMA expression to address the role of PSMA-bearing EV in promoting pro-tumoral changes in the TME using classical molecular biology and novel molecular imaging approaches.

cancer biology↗

bioRxiv2020

FRC-QE: A robust and comparable 3D microscopy image quality metric for cleared organoids

Three-dimensional stem-cell-derived organoids are a powerful tool for studying cellular processes in tissue-like structures, enabling in vitro experiments in an organ-specific context. While organoid research has been closely linked to advances in fluorescence microscopy, capturing cellular structures within their global context in an organoid often remains challenging due to the organoids dense structure and opacity. The development of optical clearing methods has provided a solution for fixed organoids but optimizing clearing protocols for a given sample type and staining can be challenging. Importantly, quantitative measures for assessing image quality throughout cleared fluorescent samples are missing. Here, we propose Fourier ring correlation quality estimation (FRC-QE) as a new metric for automated 3D image quality estimation in cleared organoids. We show that FRC-QE robustly captures differences in clearing efficiency within an organoid, across replicates and clearing protocols, as well as for different microscopy modalities. FRC-QE is open-source, written in ImgLib2 and provided as an easy-to-use and macro-scriptable plugin for the popular Fiji software. We therefore envision FRC-QE to fill the gap of providing a reliable quality metric for testing, optimizing and comparing optical clearing methods.

bioinformatics↗