Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression

Larkins, Teri; Nowell, Marchele; Singh, Shailesh; Sanford, Gary L.

doi:10.1186/1471-2407-6-181

Cited by 146 publications

(116 citation statements)

References 46 publications

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“…Recently, we found that COX-1 and COX-2 inhibitors reduced cell viability, MMP-2 and MMP-9 activities, and in vitro invasion of primary and metastatic HNSCC cells (Koontongkaew et al, 2010). Our findings are consistent with other studies that demonstrated the inhibitory effects of COX inhibitors on MMP activities in breast (Larkins et al, 2006), prostate (Attiga et al, 2000), colon (Ishizaki et al, 2006) and lung cancer cells (Karna & Palka, 2002). Regarding the role of COX-2 in the metastasis and invasion of HNSCC cells, the precise mechanism remains obscure, but a decrease of COX-2 dependent PGE 2 may downregulate MMP production through PGE 2 receptors (Dohadwala et al, 2002).…”

Section: Cox and Tumor Invasionsupporting

confidence: 92%

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

Koontongkaew¹,

Leelahavanichkul²

2012

Head and Neck Cancer

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Section: Cox and Tumor Invasionsupporting

confidence: 92%

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

Koontongkaew¹,

Leelahavanichkul²

2012

Head and Neck Cancer

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“…High COX-2 expression in breast tumors has been correlated with poor survival, distant metastasis and lower local-regional control of disease [2,3]. Ectopic expression of COX-2 in breast cancer cell lines was found to increase the production of prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8), which are essential to COX-2-induced breast cancer invasion [5][6][7]. However, which downstream factors are inhibited by the COX-2/ PGE 2 /IL-8-mediated pathway to induce breast cancer cell invasion are not known.…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

Nieves-Alicea

Colburn

Simeone

et al. 2008

Breast Cancer Res Treat

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High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE 2 and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE 2 and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE 2 and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE 2 and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE 2 and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE 2 and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.

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“…Overexpression of Her-2/Neu is now widely used by clinicians as a biomarker of poor prognosis and metastasis for patients with invasive breast cancer [167] . Molecular studies of breast cancer tissues have demonstrated that high levels of COX-2 and PGE-2 are correlated with amplified Her-2/Neu expression and increased activity of MMP [168,169] . The MMP are proteolytic enzymes that degrade basement membranes and are thus associated with tumor invasiveness, metastasis, and poor survival.…”

mentioning

confidence: 99%

Cyclooxygenase-2 and the inflammogenesis of breast cancer

Harris

Casto

Harris

2014

WJCO

151

125

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Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2 (COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following: (1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis; (2) essential features of mammary carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin E2 (PGE-2) biosynthesis; (3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis; (4) extrahepatic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and (5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic. The totality of evidence clearly supports the supposition that mammary carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the "inflammogenesis of breast cancer". Key words: Breast Cancer; Cyclooxygenase-2; Nonsteroidal anti-inflammatory drugs; Inflammogenesis; Estrogen; Aromatase Core tip: Mammary carcinogenesis often evolves as a series of highly specific cellular and molecular changes in response to induction of constitutive over-expression of cyclooxygenase-2 (COX-2) and the prostaglandin cascade; reciprocally, agents that block COX-2 have significant value in the chemoprevention and therapy of breast cancer.Harris RE, Casto BC, Harris ZM. Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol 2014; 5(4): 677-692 Available from: URL: http://www.wjgnet.com/2218-4333/full/v5/ i4/677.htm DOI: http://dx.doi.org/10.5306/wjco.v5.i4.677 INTRODUCTIONMore than a century ago, Virchow et al [1,2] chronic inflammation leads to cancer development by increasing cellular proliferation [3] . Various models of carcinogenesis have been proposed involving inflammatory stimuli and mediators of wound healing [4][5][6] . The recent discovery of the inducible cyclooxygenase-2 (COX-2) gene has rekindled interest in the causal link between inflammation and cancer, and various models of carcinogenesis have been proposed involving inflammatory stimuli and COX-2 expression [7][8][9][10] . The current review synthesizes and interprets the accumulating body of evidence supporting COX-2 driven inflammogenesis as a ge...

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Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression

Cited by 146 publications

References 46 publications

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

Cyclooxygenase-2 and the inflammogenesis of breast cancer

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