Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue

Mohammad, Mohammad Ali; Zeeneldin, Ahmed A.; Elmageed, Zakaria Y. Abd; Khalil, Ebtsam H.; Mahdy, S M El; Sharada, Hayat M.; Sharawy, Sabry; Abdel-Wahab, A.

doi:10.1007/s11010-012-1305-z

Cited by 23 publications

(12 citation statements)

References 33 publications

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“…In mammary epithelial cells, COX-2 induced an EMT featuring anchorage-independent growth [97]. In human breast cancers, COX-2 was found to induce membranetype 1-MMP and its downstream effector MMP-2 [98], factors important in EMT [99], thus providing a rational mechanism through which COX-2 can promote breast cancer invasion.…”

Section: Cox-2 Is Associated With Breast Cancer Invasion Via Emtmentioning

confidence: 99%

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

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Section: Cox-2 Is Associated With Breast Cancer Invasion Via Emtmentioning

confidence: 99%

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Hugo

Saunders

Ramsay

et al. 2015

J Mammary Gland Biol Neoplasia

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show abstract

“…The remaining 29 papers were approved through scrutinizing the entire paper. Among the 29 papers, five literatures had no sufficient data to analyze (Remacle et al, 1998;Wang et al, 2002;Casar et al, 2010;Mohammad et al, 2012;Ranogajec et al, 2012). MMP-9 protein expression was measured in serum in five studies (Lepp et al, 2004;Lepp et al, 2005;Mattilaet al, 2005;Quaranta et al, 2007;Sung et al, 2012) and one study measured MMP-9 expression in plasma (Ranuncolo et al, 2003).…”

Section: Study Characteristicsmentioning

confidence: 99%

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

Song

Su²,

Zhou³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…COX‐2 expression in predominantly ER‐negative tumors was shown to lead to Akt‐pathway activation . Regarding prognosis, most, but not all, studies have found an association between high COX‐2 expression and worse prognosis. Whether COX‐2 expression was associated with prognosis in the different studies also depended on tumor characteristics, type of breast cancer treatment, body constitution, and concomitant medications .…”

mentioning

confidence: 99%

The prognostic impact of COX‐2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size

Simonsson

Björner

Markkula

et al. 2016

Intl Journal of Cancer

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The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, adj HR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (P interaction 5 0.048), preoperative NSAID use (P interaction 5 0.009), and tumor size (P interaction 5 0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, adj HR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, adj HR 4.51 (1.18-11.44) as well as in patients with large tumors, adj HR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.Breast cancer is a heterogeneous disease where most patients have a good prognosis. Improved tumor classification could identify subgroups of patients with a poorer prognosis who are in need of more personalized treatment. 1 In breast cancer, cyclooxygenase 2 (COX-2)-mediated prostaglandin aromatase gene activation increases both aromatase and estrogen levels that may lead to increased proliferation, primarily in patients with estrogen receptor positive (ER-positive) tumors and in postmenopausal patients. 2 COX-2 catalyzes the conversion of arachidonic acid to prostaglandins and have pro-inflammatory effects. 2 COX-2 expression in predominantly ER-negative tumors was shown to lead to Akt-pathway activation. 2,3 Regarding prognosis, most, 1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] but not all, 20-27 studies have found an association between high COX-2 expression and worse prognosis. Whether COX-2 expression was associated with prognosis in the different studies also depended on tumor characteristics, type of breast cancer treatment, body constitution, and concomitant medications. 1,6 Non-steroidal anti-inflammatory drugs (NSAIDs) including both selective COX-2 inhibitors and non-selective COX-1/2 inhibitors as well as ac...

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Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue

Cited by 23 publications

References 33 publications

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

The prognostic impact of COX‐2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size

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