Diffuse Large B-Cell Lymphoma Promotes Endothelial-to-Mesenchymal Transition via WNT10A/Beta-Catenin/Snail Signaling

Area of Science:

• Oncology
• Cell Biology
• Hematology

Background:

• Diffuse Large B-cell Lymphoma (DLBCL) is a heterogeneous malignancy with high treatment failure rates.
• Endothelial-to-mesenchymal transition (EndMT) is implicated in various cancers but its role in hematological malignancies is unknown.
• Novel risk stratification and therapeutic strategies for DLBCL are critically needed.

Purpose of the Study:

• To investigate the existence and clinical relevance of EndMT in DLBCL.
• To elucidate the molecular mechanisms by which DLBCL cells induce EndMT.
• To identify potential novel biomarkers for DLBCL prognosis.

Main Methods:

• Identification of EndMT markers in DLBCL patient samples.
• In vitro co-culture experiments using DLBCL cells and human umbilical vein endothelial cells (HUVECs).
• Molecular analysis of the WNT10A/GSK3β/β-catenin/snail signaling pathway.

Main Results:

• EndMT was identified in DLBCL-associated endothelial cells and correlated with advanced stage and poor prognosis.
• DLBCL cells stimulated angiogenesis and EndMT in HUVECs.
• WNT10A overexpression in DLBCL promoted EndMT via the GSK3β/β-catenin/snail pathway, driving angiogenesis and potentially impacting clinical outcomes.

Conclusions:

• EndMT is present in DLBCL and associated with adverse clinical features.
• The WNT10A/GSK3β/β-catenin/snail pathway is a key mediator of DLBCL-induced EndMT and angiogenesis.
• EndMT markers and WNT10A may serve as novel prognostic predictors for DLBCL.