Biology subjects

Seidlits, S.

Publications and source records attributed to Seidlits, S..

4 recordsLinked to original sources

bioRxiv2026

Galectin-1 identifies a unique subpopulation of highly invasive glioblastoma cells and enables their migration

Glioblastoma (GBM), the most common primary brain tumor, is characterized by extensive infiltration into surrounding brain tissue. GBM tumors exhibit substantial intratumoral heterogeneity making it difficult to identify and target invasive cell subpopulations. Here, we use an in vitro model of the mechanical transitions at the tumor-brain interface to isolate highly invasive GBM cells from populations derived from unique patient tumors for downstream transcriptomic analysis or further culture. Using single-cell RNA sequencing combined with cell barcodes we were able to trace distinct cell lineages during migration and identify an intrinsically invasive subpopulation. This invasive subpopulation exhibits a distinct pre-invasive transcriptomic profile characterized by overexpression of galectin-1, a {beta}-galactoside binding protein. Our findings reveal galectin-1 overexpression is an innate characteristic of invasive GBM subpopulations, where expression level positively correlates with invasion rate and inhibition of galectin-1 binding to cell surface glycoproteins effectively prevented migration. While some studies have reported that galetcin-1 aids in cell migration, this study identifies and confirms that galectin-1 expression is a pre-existing characteristic of invading GBM cells and a target to prevent tumor recurrence.

Cancer Biology↗

bioRxiv2025

Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cel Adhesion to Bioactive Hydrogels

Endothelialization promotes thromboresistance in blood-contacting devices, but biomaterial designs often overlook sex differences in endothelialization processes. In this study, we elucidated sex differences in endothelial cell-material interactions through investigation of the integrin-ligand interplay with biomaterial substrates and the corollary effects on cell adhesion and spreading. First, integrin expression of human coronary artery endothelial cells (HCAECs) was characterized for age-matched donors (3 male, 3 female). Sex-based differences in integrin expression were identified, with notably higher 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells and higher 1{beta}1 expression in male cells. On polyethylene glycol (PEG)-based hydrogel incorporating collagen or gelatin, female cells showed increased attachment on stiff substrates as compared to male HCAECs, likely driven by increased 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells. Collectively, these results demonstrate sex-biased endothelial cell responses to bioactive hydrogels mediated by integrin interactions and highlight the importance of incorporating biological sex as a design variable in the development of blood-contacting biomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/656802v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@41bfb9org.highwire.dtl.DTLVardef@921619org.highwire.dtl.DTLVardef@e8df4corg.highwire.dtl.DTLVardef@9c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Ketomimetic Medium Promotes Metastatic Disposition and Chemoresistance in Breast Cancer Cells through Hypersialylation and Lipid Synthesis

While the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decode the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body-rich, low glucose) medium affects Doxorubicin (DOX) susceptibility and invasive disposition of BC cells. We quantified glycocalyx sialylation and found an inverse correlation with DOX-induced cytotoxicity and DOX internalization. These measurements were coupled with single-cell metabolic imaging, bulk migration studies, along with transcriptomic and metabolomic analyses. Our findings revealed that a ketomimetic medium enhances chemoresistance and invasive disposition of BC cells via two main oncogenic pathways: hypersialylation and lipid synthesis. We propose that the crosstalk between these pathways, juxtaposed at the synthesis of the glycan precursor UDP-GlcNAc, furthers advancement of a metastatic phenotype in BC cells under ketomimetic conditions.

cancer biology↗

bioRxiv2021

Generation of a molecular interactome of the glioblastoma perivascular niche reveals Integrin Binding Sialoprotein as a key mediator of tumor cell migration

Glioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood to the tumor, GBM vessels also provide trophic support to glioma cells and serve as conduits for migration into the surrounding brain promoting recurrence. Here, we enriched CD31-expressing glioma vascular cells (GVC) and A2B5-expressing glioma tumor cells (GTC) from primary GBM and utilized RNA sequencing to create a comprehensive interaction map of the secreted and extracellular factors elaborated by GVC that can interact with receptors and membrane molecules on GTC. To validate our findings, we utilized functional assays, including a novel hydrogel-based migration assay and in vivo mouse models to demonstrate that one identified factor, the little-studied integrin binding sialoprotein (IBSP) enhances tumor growth and promotes the migration of GTC along the vasculature. This perivascular niche interactome will serve a resource to the research community in defining the potential functions of the GBM vasculature.

cancer biology↗