Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue Mohammad A. Mohammad • Ahmed A. Zeeneldin • Zakaria Y. Abd Elmageed • Ebtsam H. Khalil • Said M. E. Mahdy • Hayat M. Sharada • Sabry K. Sharawy • Abdel-Hady A. Abdel-Wahab Received: 12 September 2011 / Accepted: 3 April 2012 / Published online: 18 April 2012 Ó Springer Science+Business Media, LLC. 2012 Abstract Breast cancer (BC) is the most common neo- plasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognos- tic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, dis- ease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP- 2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clini- copathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors. Keywords Breast cancer Á Cox-2 Á MMPs Á MT1-MMP Á Western blot Á Zymography Introduction Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide with an estimated 1.4 million new BC cases and 458,000 deaths in 2008 [1]. The main contributing factor to the rising mortality rate is the spread of distant metastases to different organs [2]. Higher incidence of BC in urban and more developed populations in Egypt was recently reported and this problem is usually linked to continuous exposure to xenoes- trogens, endocrine disruptors or genotoxic substances [3]. It is reported that BC represents about 37 % of all female cancers hospitalized in the National Cancer Institute of Egypt [4]. Cyclooxygenase (COX) is proved to convert membrane arachidonic acid into prostaglandins where their target effects were determined by G protein-coupled receptors [5]. COX-2 is well known to be involved in precursor M. A. Mohammad Á S. K. Sharawy Á A.-H. A. Abdel-Wahab (&) Department of Cancer Biology, National Cancer Institute, Cairo University, 1 Kasr El-Aini St, Cairo, Egypt e-mail: abdelhadya@gmail.com A. A. Zeeneldin Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Z. Y. Abd Elmageed Department of Urology and Oncology, Tulane University Medical Center, New Orleans, LA 70112, USA E. H. Khalil Á S. M. E. Mahdy Á H. M. Sharada Department of Chemistry, Faculty of Science, Helwan University, Helwan, Egypt 123 Mol Cell Biochem (2012) 366:269–275 DOI 10.1007/s11010-012-1305-z