UNASSIGNED: The @entity5 microenvironment is critical to @entity5 growth and therapy resistance. We previously characterized @entity1 ovarian @entity1358 ( @entity1358 ). @entity1358 are multi-potent cells that can differentiate into @entity5 microenvironment components including fibroblasts, myofibroblasts and adipocytes. We previously reported @entity1358 , compared to normal MSCs, express high levels of @entity6861 proteins and promote @entity5 growth by increasing numbers of @entity5 stem-like cells (CSCs). We demonstrate here that @entity43 cell-secreted Hedgehog (HH) induces CA-MSC @entity13062 expression. CA-MSC-derived @entity13062 reciprocally increases @entity43 cell HH expression indicating a positive feedback loop. Interruption of this loop with a HH pathway inhibitor or @entity13062 blocking antibody decreases CA-MSC-derived @entity13062 and @entity5 -derived HH preventing enrichment of CSCs and reversing chemotherapy resistance. The impact of HH inhibition was only seen in CA-MSC-containing @entity5 , indicating the importance of a humanized stroma. These results are reciprocal to findings in pancreatic and @entity150 , suggesting HH signaling effects are @entity5 tissue specific warranting careful investigation in each @entity5 type. Collectively, we define a critical positive feedback loop between CA-MSC-derived @entity13062 and @entity43 cell-secreted HH and present evidence for the further investigation of HH as a clinical target in @entity43 .

@entity1 XXXX promote @entity43 chemotherapy resistance via a @entity13062 /HH signaling loop.

@entity1 :: ('9606', 'Species') :: ['human'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian tumor', 'ovarian cancer'] @entity13062 :: ('652', 'Gene') :: ['BMP4'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity1358 :: ('MESH:D002292', 'Disease') :: ['CA-MSCs', 'carcinoma-associated mesenchymal stem cells'] @entity150 :: ('MESH:D001749', 'Disease') :: ['bladder cancer'] @entity6861 :: ('649', 'Gene') :: ['BMP']
@entity1358 :: (MESH:D002292,Disease) :: ['carcinoma-associated mesenchymal stem cells']
