Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.
Mol Oncol
; 2024 Sep 08.
Article
en En
| MEDLINE
| ID: mdl-39245631
ABSTRACT
Alpha-smooth muscle actin (α-SMA) expression in the stroma is linked to the presence of cancer-associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α-SMA-expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3). Selected regions of interest were segmented geometrically based on tissue morphology and fluorescent signals from synaptophysin and α-SMA markers. The α-SMA-expressing stromal-cell-associated genes were involved in pathways of extracellular matrix modification, whereas, in tumor cells, the gene expression profiles were associated with pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that the differences between grades are not only present at the level of the tumor but also in the α-SMA-expressing stromal cells. Furthermore, the tumor cells from regions with a rich presence of adjacent α-SMA-expressing stromal cells revealed an upregulation of matrix metalloproteinase-9 (MMP9) expression in grade 3 tumors. This study provides an in-depth characterization of gene expression profiles in α-SMA-expressing stromal and tumor cells, and outlines potential crosstalk mechanisms.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Letonia
Pais de publicación:
Estados Unidos