Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP‐9 induction

Kummer, Nicolas; Nowicki, Theodore S.; Azzi, J.-P.; Reyes, Ismael; Iacob, Codrin; Xie, Suqing; Swati, Ismatun; Darzynkiewicz, Zbigniew; Gotlinger, Katherine; Suslina, Nina; Schantz, Stimson P.; Tiwari, Raj K.; Geliebter, Jan

doi:10.1002/jcb.24069

Cited by 48 publications

(47 citation statements)

References 38 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased expression levels of MMPs are associated with a number of cancers. Recent study demonstrates that arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP‐9 induction . There is compelling evidence to suggest that MMP9 plays important roles in tumor invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasionviaactivation of PI3K/Akt/NF-κB

et al. 2013

View full text Add to dashboard Cite

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of death in males in the United States. Using human prostate cancer specimens, the authors have previously shown that elevated expression levels of 12-lipoxygenase (12-LOX) occurred more frequently in advanced stage, high-grade prostate cancer, suggesting that 12-LOX expression is associated with carcinoma progression and invasion. Previous reports from their group and others have shown that 12-LOX is a positive modulator of invasion and metastasis; however, the mechanism remains unclear. In this work, a new link between 12-LOX and the matrix metalloproteinase 9 (MMP9) in prostate cancer angiogenesis is reported. This study demonstrated that overexpression of 12-LOX in prostate cancer PC-3 cells resulted in elevated expression of MMP9 mRNA, protein and secretion. Exogenous addition of 12(S)-hydroxy eicosatetraenoic acid, the sole and stable end product of arachidonic acid metabolism by 12-LOX, is able to increase MMP9 expression in wild-type PC-3 cells. Furthermore, using pharmacological and genetic inhibition approaches, it was found that 12-LOX activates phosphoinositol 3 kinase (PI3K)/Akt, which results in nuclear factor-kappa B (NF-κB)-driven MMP9 expression, ensuing in enhanced chemoattraction of endothelial cells. Specific inhibitors of 12-LOX, PI3K or NF-κB inhibited MMP9 expression in 12-LOX-expressing PC-3 cells and resulted in the blockade of the migratory ability of endothelial cells. In summary, the authors have identified a new pathway by which overexpression of 12-LOX in prostate cancer cells leads to augmented production of MMP9 via activation of PI3K/Akt/NF-κB signaling. The role of 12-LOX-mediated MMP9 secretion in endothelial cell migration may account for the proangiogenic function of 12-LOX in prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Recent study demonstrates that arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP-9 induction. 27 There is compelling evidence to suggest that MMP9 plays important roles in tumor invasion and metastasis. The design of new drugs to inhibit MMP expression levels is, therefore, a priority.…”

Section: Discussionmentioning

confidence: 99%

Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasionviaactivation of PI3K/Akt/NF-κB

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Few studies showed that 5-HETE promoted cancer cell migration by increasing the expression of MMP-9. 41 However, we found that 5-LOX metabolites from hypoxic ovarian cancer cells enhanced the expression of MMP-7 to promote the invasion of macrophages. Besides, MMP-7 was also highly expressed in macrophages close to the hypoxic area in the human ovarian tumor.…”

Section: Discussionmentioning

confidence: 97%

Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration

Wen

Liu

et al. 2014

Oncogene

View full text Add to dashboard Cite

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.

show abstract

“…1 A small number of studies have recently suggested that 5-LO pathway metabolites are involved in the progression of various types of cancer, including prostate cancer, 2,3 pancreatic cancer, 4 esophageal cancer, 5 hepatocellular carcinoma, 6 and papillary thyroid carcinoma. 7 Recent studies have reported the strong immunoreactivity of 5-LO in Purkinje neurons, certain glial cells in the cerebellum, and parts of brain tumors. 8,9 Currently, no reports have been made on the immunoreactivity status of 5-LO in normal and neoplastic tissues of the human choroid plexus.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies have used immunohistochemistry to show cytoplasmic staining for 5-LO in a subset of cells in CNS tumors. 7,9 Researchers have suggested that a decrease in LT C4 synthesis or increase in interleukin 5 could trigger the translocation of 5-LO to the nucleus in human blood eosinophils, 21,22 but the mechanism of this translocation between nucleus and cytoplasm in tumor cells remains unclear. In this study, we found that most types of brain tumors, including astrocytic, oligodendrogliomatous, ependymal, embryonal, and meningeal tumors, exhibited predominantly nuclear 5-LO staining, with weakly positive cytoplasmic staining in a small number of cases.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic 5-Lipoxygenase Staining Is a Highly Sensitive Marker of Human Tumors of the Choroid Plexus

Wang

Zhang²,

Yupeng

et al. 2015

American Journal of Clinical Pathology

View full text Add to dashboard Cite

show abstract

Arachidonate 5 lipoxygenase expression in papillary thyroid carcinoma promotes invasion via MMP‐9 induction

Cited by 48 publications

References 38 publications

Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasionviaactivation of PI3K/Akt/NF-κB

Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasionviaactivation of PI3K/Akt/NF-κB

Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration

Cytoplasmic 5-Lipoxygenase Staining Is a Highly Sensitive Marker of Human Tumors of the Choroid Plexus

Contact Info

Product

Resources

About