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Endoglin and squamous cell carcinomas.

Sarah K Hakuno1, Stefanus G T Janson1, Marjolijn D Trietsch2,3

  • 1Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, Netherlands.

Frontiers in Medicine
|July 3, 2023
PubMed
Summary
This summary is machine-generated.

Endoglin is expressed on squamous cell carcinoma (SCC) cells, influencing paracrine signaling but not directly affecting cancer cell proliferation or migration. This study clarifies endoglin's role in head and neck, esophageal, and vulvar cancers.

Keywords:
BMP-9TGF-βTRC105endoglinsquamous cell carcinoma

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Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • Endoglin's role on endothelial cells is well-defined, but its expression and function on epithelial cancer cells, particularly squamous cell carcinoma (SCC), remain unclear.
  • Investigating endoglin in SCC is crucial for understanding cancer biology and potential therapeutic targets.

Purpose of the Study:

  • To determine the expression and functional role of endoglin in head and neck (HNSCC), esophageal (ESCC), and vulvar (VSCC) squamous cell carcinoma.
  • To elucidate endoglin's involvement in TGF-β signaling pathways within SCC cells.

Main Methods:

  • Tumor specimens and 14 patient-derived SCC cell lines were analyzed for endoglin expression.
  • Endoglin was overexpressed, knocked out, or its signaling blocked using the TRC105 antibody to assess functional impact.
  • BMP-9 induced SMAD1 phosphorylation was measured to evaluate TGF-β pathway activity.

Main Results:

  • Endoglin is selectively expressed by individual SCC cells within tumor nests, with significant interpatient variation in expression levels across HNSCC, ESCC, and VSCC cell lines.
  • BMP-9 signaling led to SMAD1 phosphorylation, independent of ALK1 receptor expression.
  • Endoglin overexpression increased soluble endoglin levels, subsequently reducing BMP-9 signaling; however, endoglin did not directly affect SCC cell proliferation or migration.

Conclusions:

  • Endoglin is expressed on individual SCC cells in tumor nests, playing a role in paracrine signaling.
  • Soluble endoglin modulates BMP-9 signaling, but endoglin does not directly influence SCC proliferation or migration in an autocrine manner.