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286252 occurrences (No.88 in the rank) during 5 years in the PubMed. [no cache] 500 found
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286252 occurrences (No.88 in the rank) during 5 years in the PubMed. [no cache] 500 found
| 219) In this study, we found that the expression of 5-LOX strongly correlated with the density of TAMs in hypoxic areas of human ovarian tumor tissues. |
| PMID:24662827 DOI:10.1038/onc.2014.85 |
| 2015 Oncogene |
| * Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration. |
| - 5-lipoxygenase (5-LOX), a member of the lipoxygenase gene family, is a key enzyme assisting in the conversion of arachidonic acid to 5-HETE and leukotrienes. Tumor-associated macrophages (TAMs) have a critical role in the progression and metastasis of many tumors, including ovarian tumors. Moreover, TAMs are often found in a high density in the hypoxic areas of tumors. However, the relevant mechanisms have not been studied explicitly until now. In this study, we found that the expression of 5-LOX strongly correlated with the density of TAMs in hypoxic areas of human ovarian tumor tissues. In cultured ovarian cancer cells, 5-LOX metabolites were increased under hypoxic conditons. Increased 5-LOX metabolites from hypoxic ovarian cancer cells promoted migration and invasion of macrophages, which was further demonstrated to be mediated by the upregulation of matrix metalloproteinase (MMP)-7 expression through the p38 pathway. Besides, we also showed that 5-LOX metabolites enhanced the release of tumor necrosis factor (TNF-α) and heparin-binding epidermal growth factor-like growth factor through upregulation of MMP-7. Furthermore, in animal models, Zileuton (a selective and specific 5-LOX inhibitor) reduced the MMP-7 expression and the number of macrophages infiltrating in the xenograft. Our findings suggest for the first time that increased metabolites of 5-LOX from hypoxic ovarian cancer cells promote TAM infiltration. These results of this study have immediate translational implications for the therapeutic exploitation of TAMs. |
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(16)3 multiple |
(30)2 P2X3 |
(45)2 constitutively |
| (3)9 genes |
(17)3 ncRAN |
(32)2 Sema |
(46)2 hyaluronan |
| (4)8 several |
(18)3 nicotine-induced |
(33)2 Siglec-9 |
(47)2 imprinted |
| (5)6 miR-218 |
(19)3 nuclear |
(34)2 TAF4 |
(48)2 intercellular |
| (6)5 these |
(20)3 specific |
(35)2 Wnt |
(49)2 membrane |
| (7)4 VEGF |
(21)3 this |
(36)2 acetyl-CoA |
(50)2 miR-128 |
| (8)4 first |
(22)2 AdipoR1 |
(37)2 adhesion |
(51)2 napsin |
| (9)4 matrix |
(23)2 Caspase |
(38)2 adiponectin |
(52)2 phosphorylated |
| (10)3 CYP1A1 |
(24)2 FBP1 |
(39)2 angiogenic |
(53)2 piRNA-823 |
| (11)3 DNMT1 |
(25)2 GABAA |
(40)2 anti-apoptotic |
(54)2 pro-inflammatory |
| (12)3 all |
(26)2 GLP-1R |
(41)2 b-FGF, |
(55)2 some |
| (13)3 cardiac |
(27)2 Ki-67, |
(42)2 c-Myc |
(56)2 three |
| (14)3 integrin |
(28)2 LOX-1 |
(43)2 cartilage |
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