Secretomes From Non-Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial...

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• The tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) is complex and influences tumor growth and treatment resistance.
• Endothelial cells (ECs) within the TME can undergo endothelial-to-mesenchymal transition (EndMT), contributing to cancer progression and therapeutic resistance.
• EndMT involves ECs losing their endothelial characteristics and acquiring a mesenchymal phenotype, promoting the development of cancer-associated fibroblasts (CAFs).

Purpose of the Study:

• To investigate the effects of various lung tumor secretomes on the phenotype and plasticity of endothelial cells.
• To understand how exposure to different tumor-derived factors influences endothelial cell behavior and potential EndMT induction.

Main Methods:

• Conditioned media (CM) were generated from five distinct NSCLC cell lines.
• Human umbilical vein endothelial cells (HUVECs) were treated with these CMs.
• Assays included proliferation (Cyquant), migration (Incucyte), tubulogenesis (Matrigel), flow cytometry for phenotypic markers, immunohistochemistry for actin fibers, and mass spectrometry for secretome proteomic analysis.

Main Results:

• Treatment with tumor secretomes induced significant phenotypic changes in HUVECs, characterized by altered morphology and increased stress fiber expression.
• A notable increase in spontaneous migration and mesenchymal markers (α-SMA, CD44) was observed, confirming partial EndMT.
• However, the rate of cells expressing both endothelial and mesenchymal markers (vWF+/α-SMA+ or CD31+/CD44+) did not increase, indicating incomplete transition.

Conclusions:

• Lung tumor secretomes can induce a partial endothelial-to-mesenchymal transition (EndMT) in endothelial cells.
• The identified phenotypic and molecular changes highlight the plasticity of ECs within the TME.
• Proteomic analysis revealed potential therapeutic targets associated with EndMT, offering avenues for future NSCLC treatment strategies.