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Peer-reviewedCC BY 4.0Cells

SPP1-CD44-Mediated Crosstalk Between Endothelial and Macrophage Subpopulations Promotes Pancreatic Ductal Adenocarcinoma Progression Through S100A6 Upregulation

  • Yanbin Zhou1
  • Sixian Guo2,3
  • Wenhu Zhou1,4
  • Wei Wang1
4 affiliations
  1. 1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
  2. 2School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
  3. 3Faculty of Chinese Medicine, Medical Sciences Division, Macau University of Science and Technology, Macau 999078, China
  4. 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha 410219, China
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) progression is driven by complex cellular interactions within the tumor microenvironment (TME), where endothelial cell (EC)-tumor-associated macrophage (TAM) crosstalk significantly influences angiogenesis and immune modulation, although the specific subsets and consequences remain unclear. Here, we integrated four single-cell RNA sequencing datasets (50 PDAC; 21 normal adjacent tissues) to profile EC and macrophage subpopulations, subsequently employing CellChat to decipher intercellular communication networks and identify altered ligand–receptor interactions in PDAC. Correlation and Kaplan–Meier survival analyses (TCGA-PAAD) assessed associations and prognostic value, while functional validation used EdU, CCK-8, and Transwell assays on PDAC cells. We identified a distinct endothelial subset (EC0) and macrophage subset (Mac2) with enhanced interaction signals in PDAC. This EC0–Mac2 crosstalk correlated with significant S100A6 upregulation, which was associated with poor patient prognosis. Exogenous S100A6 treatment markedly enhanced PDAC cell proliferation and migration in vitro. In conclusion, EC-Mac crosstalk may promote PDAC progression via S100A6, and this interaction pattern warrants further investigation as a candidate prognostic biomarker and potential target for disrupting stromal communication.

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Cite

BibTeXRIS
BibTeX
@article{zhou2026spp1cd44mediated,
  title = {{SPP1-CD44-Mediated Crosstalk Between Endothelial and Macrophage Subpopulations Promotes Pancreatic Ductal Adenocarcinoma Progression Through S100A6 Upregulation}},
  author = {Yanbin Zhou and Sixian Guo and Wenhu Zhou and Wei Wang},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15201844},
  url = {https://www.mdpi.com/2073-4409/15/20/1844},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - SPP1-CD44-Mediated Crosstalk Between Endothelial and Macrophage Subpopulations Promotes Pancreatic Ductal Adenocarcinoma Progression Through S100A6 Upregulation
AU  - Yanbin Zhou
AU  - Sixian Guo
AU  - Wenhu Zhou
AU  - Wei Wang
PY  - 2026
DA  - 2026/10/11
JO  - Cells
DO  - 10.3390/cells15201844
UR  - https://www.mdpi.com/2073-4409/15/20/1844
AB  - Pancreatic ductal adenocarcinoma (PDAC) progression is driven by complex cellular interactions within the tumor microenvironment (TME), where endothelial cell (EC)-tumor-associated macrophage (TAM) crosstalk significantly influences angiogenesis and immune modulation, although the specific subsets and consequences remain unclear. Here, we integrated four single-cell RNA sequencing datasets (50 PDAC; 21 normal adjacent tissues) to profile EC and macrophage subpopulations, subsequently employing CellChat to decipher intercellular communication networks and identify altered ligand–receptor interactions in PDAC. Correlation and Kaplan–Meier survival analyses (TCGA-PAAD) assessed associations and prognostic value, while functional validation used EdU, CCK-8, and Transwell assays on PDAC cells. We identified a distinct endothelial subset (EC0) and macrophage subset (Mac2) with enhanced interaction signals in PDAC. This EC0–Mac2 crosstalk correlated with significant S100A6 upregulation, which was associated with poor patient prognosis. Exogenous S100A6 treatment markedly enhanced PDAC cell proliferation and migration in vitro. In conclusion, EC-Mac crosstalk may promote PDAC progression via S100A6, and this interaction pattern warrants further investigation as a candidate prognostic biomarker and potential target for disrupting stromal communication.
SN  - 2073-4409
ER  -