Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target...

Area of Science:

• Extracellular vesicle biology
• Cancer research
• Molecular oncology

Background:

• Tumor cell-derived extracellular vesicles (TEX) influence the tumor microenvironment.
• The role of TEX in target cell reprogramming is not fully understood.
• Specific tetraspanins on TEX, like Tspan8, are implicated in angiogenesis and premetastatic niche formation.

Purpose of the Study:

• To investigate how TEX alter mRNA and miRNA profiles in rat endothelial cells (EC) and lung fibroblasts (Fb).
• To explore the role of Tspan8 expression in TEX-mediated cellular responses.
• To elucidate the contribution of long noncoding RNAs (lncRNAs) in TEX-induced target cell reprogramming.

Main Methods:

• Coculture of rat EC and Fb with TEX derived from BSp73AS and BSp73ASML tumor lines (modified for Tspan8 expression or knockdown).
• Deep sequencing for mRNA profiling and array analysis for miRNA profiling of EC and Fb before and after TEX coculture.
• Analysis of signaling molecule and transcription factor activation, and lncRNA involvement.

Main Results:

• EC and Fb showed more robust responses to TEX expressing higher levels of Tspan8.
• Both cell types exhibited upregulation and activation of signaling molecules and transcription factors upon TEX interaction.
• TEX-induced miRNA profile changes were partly mediated by lncRNAs, affecting chromosome organization and mRNA processing.

Conclusions:

• TEX activate autonomous programs within target cells, initiated by specific TEX components.
• Cellular responses to TEX are target cell-specific.
• The significant impact of lncRNAs highlights their role in TEX-mediated target cell remodeling through shuttling and location-dependent functions.