GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE247072 Query DataSets for GSE247072
Status Public on Dec 01, 2023
Title Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The sparse vascularity of Pancreatic Ductal Adenocarcinoma (PDAC) presents a mystery: what prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell types in vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of non-canonical WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues.
Overall design To investigate cell specific changes upon in vivo Smoothened inhibition, tumor bearing KPC mice were treated with either IPI-926 or vehicle for two days and collected tumor tissue for single cell RNA sequencing.
We then performed single cell regulatory network analysis, with a focus on the activity of Hedgehog, WNT, and VEGF signaling pathways.
Contributor(s) Hasselluhn MC, Decker-Farrell AR, Vlahos L, Thomas DH, Curiel-Garcia A, Maurer CH, Wasko UN, Tomassoni L, Sastra SA, Palermo CF, Dalton TC, Ma A, Li F, Tolosa EJ, Hibshoosh H, Fernandez-Zapico ME, Muir A, Califano A, Olive KP
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Nov 06, 2023
Last update date Dec 01, 2023
Contact name Lukas Vlahos
Organization name Columbia University
Department Systems Biology
Lab Andrea Califano
Street address 1130 St Nicholas Ave
City New York City
State/province New York
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM7882922 Pancreatic Tumor Tissue, IPI-926, 2 days, KA003
GSM7882923 Pancreatic Tumor Tissue, IPI-926, 2 days, KA005
GSM7882924 Pancreatic Tumor Tissue, vehicle, 2 days, KA006
BioProject PRJNA1036165

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE247072_RAW.tar 496.9 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap