Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P05109 (
S100A8
)
1,212
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acquired resistance to chemotherapy remains a major stumbling block in cancer treatment. Chronic inflammation has a crucial role in induction of chemoresistance and results, in part, from the induction and expansion of inflammatory cells that include myeloid-derived suppressor cells (MDSCs) and IL-13
+
Th2 cells. The mechanisms that lead to induction of activated MDSCs and IL-13
+
Th2 cells have not yet been identified. Here we demonstrated that doxorubicin (DOX) treatment of 4T1 breast tumor-bearing mice led to the induction of IL-13R
+
miR-126a
+
MDSCs (DOX-MDSC). DOX-MDSC promote breast tumor lung metastasis through MDSC miR-126a
+
exosomal-mediated induction of IL-13
+
Th2 cells and
tumor angiogenesis
. The induction of DOX-MDSC is regulated in a paracrine manner. DOX treatment not only increases interleukin (IL)-33 released from breast tumor cells, which is crucial for the induction of IL-13
+
Th2 cells, but it also participates in the induction of IL-13 receptors and miR-126a expressed on/in the MDSCs. IL-13 released from IL-13
+
Th2 cells then promotes the production of DOX-MDSC and MDSC miR-126a
+
exosomes via MDSC IL-13R. MDSC miR-126a
+
exosomes further induce IL13
+
Th2 cells in a positive feed-back loop manner. We also showed that MDSC miR-126a rescues DOX-induced MDSC death in a
S100A8
/A9-dependent manner and promotes
tumor angiogenesis
. Our findings provide insight into the MDSC exosomal-mediated chemoresistance mechanism, which will be useful for the design of inhibitors targeting the blocking of induction of miR-126a
+
MDSCs.
...
PMID:Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis. 2734 2
