Megalin (LRP2) Expression Patterns in Prostate Cancer Stem Cells and Metastatic Subtypes: Implications for Tumor...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Megalin (LRP2) is an endocytic receptor with an understudied role in prostate cancer (PCa).
• Its function in cancer stem cells (CSCs) and metastatic progression is largely unknown.
• Investigating LRP2 is crucial for understanding PCa development and spread.

Purpose of the Study:

• To investigate the expression patterns of Megalin (LRP2) in prostate cancer cells and clinical samples.
• To explore the correlation of LRP2 with cancer stem cell markers (CD133, CD44) and metastatic progression.
• To identify potential metabolic pathways and gene interactions involving LRP2 in PCa.

Main Methods:

• LRP2, CD133, and CD44 expression analyzed in PCa cell lines (DU-145, PC-3) and CSCs using qRT-PCR and immunofluorescence in 2D/3D cultures.
• Public RNA-seq datasets (TCGA, WCDT-MCRPC) utilized to examine LRP2 expression in normal, primary, and metastatic tumors.
• Gene Set Enrichment Analysis (GSEA) and correlation analyses performed with androgen receptor (AR), vitamin D receptor (VDR), and stemness genes.

Main Results:

• LRP2 expression was upregulated in DU-145 cells/CSCs (3D culture) but downregulated in PC-3 CSCs.
• Clinical data revealed significantly higher LRP2 levels in metastatic tumors compared to primary tumors, particularly in bone (M1B) and other sites (M1C).
• CD133 expression was consistently lower in metastases; GSEA indicated LRP2's involvement in lipid, retinoid, and steroid metabolism, with correlations to VDR and AR in M1C tumors.

Conclusions:

• LRP2 exhibits subtype-specific expression in PCa, with increased levels in DU-145 CSCs and metastatic tissues.
• The association of LRP2 with metabolic pathways and its inverse correlation with AR suggest a role in therapy resistance.
• LRP2 may be a key player in prostate cancer metastasis and treatment outcomes.