Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours

Abstract

Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL–MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1–2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients’ age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-014-1579-y) contains supplementary material, which is available to authorized users.

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

“…Similarly, ficolin‐1 (M‐ficolin) has been associated with colorectal cancer, and serum concentrations of ficolin‐2 (L‐ficolin) and ficolin‐3 (H‐ficolin) have been found to be increased in patients with malignant ovarian tumors compared to benign tumors or normal ovaries . Also, MBL concentration has been found to be increased in patients with colorectal cancer, advanced ovarian cancer, glioblastoma multiforme and thyroid cancer …”

Genetic variants and risk of esophageal squamous cell carcinoma: A GWAS-based pathway analysis

“…The second strongest mechanism involved the modulation of monosaccharide binding that selectively interacts with any monosaccharide by rs1800450, which may alter the expression of Mannan-Binding Lectin 2 (MBL2). Mannan-binding lectin (MBL), which encodes the soluble mannose-binding lectin or mannose-binding protein found in serum, is a member of the collectin family and plays an important role in the innate immune system (Swierzko et al, 2014). It can act directly as an opsonin or activating MBL-associated serine proteases (MASPs), thus initiating the antibody-independent pathway of the complement system.…”

Lectin pathway factors in patients suffering from juvenile idiopathic arthritis

“…Serum MBL was assayed both by the standard method based on mannan‐binding activity (‘serum MBL’) and by its ability to activate complement (‘MBL–MASP‐2 complex activity’). Serum MBL, 49 ficolin‐3 47 concentrations and MBL–MASP‐2 complex activities 50 were measured by enzyme‐linked immunosorbent assay as described before. Briefly, mannan from Saccharomyces cerevisiae (prepared by alkaline extraction, Sigma‐Aldrich, St Louis, MO, USA) was used for coating, whereas murine anti‐human MBL mAbs (clone HYB 131‐01; BioPorto, Hellerup, Denmark) or rabbit polyclonal anti‐human C4c antibodies (Dako, Glostrup, Denmark) and corresponding horseradish peroxidase‐conjugated secondary antibodies were used for detection of MBL or C4 activation products, respectively.…”

“…Patients with MBL serum concentrations <150 ng ml −1 (or MBL‐MASP‐2 activity <75 mU ml −1 ) were considered deficient 50 . Concentrations of ficolin‐1, ficolin‐2, ficolin‐3 and MASP‐2 lower than values corresponding to the 10th percentiles determined for the control group (0.8, 1.9, 11.8 and 170 ng ml −1 , respectively) were considered ‘low’.…”