| RRC ID |
59763
|
| Author |
Dai J, Escara-Wilke J, Keller JM, Jung Y, Taichman RS, Pienta KJ, Keller ET.
|
| Title |
Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis.
|
| Journal |
J Exp Med
|
| Abstract |
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 bone marrow stromal cells (BMSCs) as a novel mechanism through which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in a HIF-1α-dependent fashion, which subsequently enhances PCa seeding and growth in the bone marrow. Furthermore, serum-derived exosomes from patients with either primary PCa or PCa metastasis, as opposed to healthy men, reveal that increased exosome PKM2 expression is associated with metastasis, suggesting clinical relevance of exosome PKM2 in PCa. Targeting the exosome-induced CXCL12 axis diminished exosome-mediated bone metastasis. In summary, primary PCa cells educate the bone marrow to create a premetastatic niche through primary PCa exosome-mediated transfer of PKM2 into BMSCs and subsequent up-regulation of CXCL12. This novel mechanism indicates the potential for exosome PKM2 as a biomarker and suggests therapeutic targets for PCa bone metastasis.
|
| Volume |
216(12)
|
| Pages |
2883-2899
|
| Published |
2019-12-2
|
| DOI |
10.1084/jem.20190158
|
| PII |
jem.20190158
|
| PMID |
31548301
|
| PMC |
PMC6888980
|
| MeSH |
Animals
Bone Neoplasms / secondary*
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemokine CXCL12 / genetics
Chemokine CXCL12 / metabolism
Disease Models, Animal
Exosomes / metabolism*
Gene Expression
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Male
Mice
Models, Biological
Prostatic Neoplasms / immunology
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology*
Pyruvate Kinase / genetics
Pyruvate Kinase / metabolism*
Stromal Cells / immunology
Stromal Cells / metabolism*
Tumor Burden
|
| IF |
10.892
|
| Times Cited |
8
|
| Resource |
| Human and Animal Cells |
ST2(RCB0224) |
