Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease

Abstract

BackgroundRecent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.MethodsThe study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.ResultsWomen with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.ConclusionThese findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

Fingerprinting of gelatinase subtypes for different topographic regions on non-retaining placenta of Holstein cows

“…The frequency of detection of NGAL-MMP-9 complex, along with other high molecular weight MMP species, was significantly higher in urine from prostate and bladder cancer groups than controls (Roy et al, 2008). Women with invasive ductal carcinoma exhibited significantly increased blood levels of MMP-9, NGAL and NGAL-MMP-9 complex compared with healthy controls (Provatopoulou et al, 2009). NGAL-MMP-9 complex was detected in over 80% of the urine samples from breast cancer patients but none in those from healthy age-and sexmatched controls (Fernandez et al, 2005).…”

“…In this study, we used gelatin zymography to measure the expression level of gelatinase subtypes on different topographic locations of non-retaining cow placenta. Because the high expression level of MMP in tissues is generally accompanied with high MMP level in body fluids (Roy et al, 2008;Provatopoulou et al, 2009), we concomitantly estimated the gelatinase subtypes in different body fluids from cows and neonatal calves. The methodology has been verified for optimal visualization of most of the gelatinase species on zymograms (Figure 2), where 7-µg protein equivalent of fluid volume or 10-µg protein equivalent of tissue extracts were subjected to analysis.…”

“…Nonetheless, NGAL-MMP-9 complex seemed to express relatively higher in fluids (Figure 3) and the umbilical cord ( Figure 6) with greater frequency (Figure 7) compared with the placenta tissue itself. Serum and urine levels of NGAL-MMP-9 complex have been evaluated for their diagnostic and prognostic values in a variety of diseases (Fernandez et al, 2005;Roy et al, 2008;Provatopoulou et al, 2009). The frequency of detection of NGAL-MMP-9 complex, along with other high molecular weight MMP species, was significantly higher in urine from prostate and bladder cancer groups than controls (Roy et al, 2008).…”

“…Statistical analyses Statistics for this study consulted that of Thomas et al (2002) and Provatopoulou et al (2009) and the Student t-test of SAS Institute (2008) was performed to compare the difference in gelatinase level between topographic regions. P-value < 0.05 was regarded statistically significant.…”

“…They have been suggested to participate in the remodeling and ECM breakdown of the uterus during estrus cycle, placentation, implantation, gestation and periparturient in different species (Walter and Boos, 2001;Uekita et al, 2004;Demir-Weusten et al, 2007;Kizaki et al, 2008;McNaughton and Murray, 2009). Multiple forms of MMP-2 and -9 are present physiologically varying in molecular size and functionality, such as the low molecular weight MMP-2 species of 68, 64 and 60 kDa, respectively (Maj and Kankofer, 1997;Kizaki et al, 2008) and the high molecular weight MMP-9 species of 125 kDa (neutrophil gelatinase-associated lipocalin-MMP-9, NGAL-MMP-9), 140 kDa (MMP-9-tissue inhibitor of metalloproteinase, MMP-9-TIMP-1) and 220 kDa (MMP-9 dimmer), respectively (Fernandez et al, 2005;Roy et al, 2008;Provatopoulou et al, 2009). NGAL or lipocalin 2 is a prominent member of the lipocalin family (Kjeldsen et al, 1993) capable of binding hydrophobic molecules.…”