Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis

• DOI: 10.1084/jem.20190158
• Publication Date: 2019-09-23T19:04:12Z
• Authors: Jinlu Dai; June Escara-Wilke; Jill M. Keller; Younghun Jung; Russell S. Taichman; Kenneth J. Pienta; Evan T. Keller
• Keywords: Exosome; PKM2

Prostate cancer (PCa) metastasizes selectively to bone through unknown mechanisms. In the current study, we identified exosome-mediated transfer of pyruvate kinase M2 (PKM2) from PCa cells into marrow stromal (BMSCs) as a novel mechanism which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in HIF-1α-dependent fashion, subsequently enhances seeding and growth marrow. Furthermore, serum-derived patients with either or metastasis, opposed healthy men, reveal increased exosome expression is associated suggesting clinical relevance PCa. Targeting exosome-induced axis diminished metastasis. summary, educate create BMSCs subsequent up-regulation CXCL12. This indicates potential for biomarker suggests therapeutic targets