Lymphatic endothelial cells actively regulate prostate cancer cell invasion

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Lymphatic vessels are key routes for cancer metastasis.
• The impact of cancer cell and lymphatic endothelial cell (LEC) interactions, especially in hypoxic conditions, on cancer cell invasion remains unclear.

Purpose of the Study:

• To investigate the role of LEC-prostate cancer (PCa) cell interactions in extracellular matrix (ECM) invasion and degradation.
• To determine metabolic changes in PCa cells under normoxia and hypoxia in the presence of LECs.

Main Methods:

• Utilized an MR-compatible cell perfusion assay.
• Examined two human PCa cell lines (PC-3 and DU-145) and human dermal lymphatic microvascular endothelial cells (HMVEC-dlys).
• Assessed invasion, ECM degradation, enzyme activity (MMP-9), gene expression (uPAR), and metabolite profiles under normoxia and hypoxia.

Main Results:

• HMVEC-dlys presence significantly increased ECM invasion and degradation by invasive PC-3 cells, partly due to elevated MMP-9 activity.
• PC-3 cells showed higher uPAR and MMP-9 expression than DU-145 cells, correlating with increased invasion.
• Hypoxia reduced PC-3 cell invasion, but this effect was attenuated by HMVEC-dlys.
• Hypoxia induced lipid accumulation in both cell lines as a survival response.

Conclusions:

• Interactions between invasive PCa cells and LECs enhance cancer cell invasion and ECM degradation, promoting metastasis.
• MMP-9 and uPAR expression are critical factors in PCa cell invasiveness.
• Hypoxia's inhibitory effect on invasion is modulated by LEC interaction, suggesting complex in vivo dynamics.