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.
Highlights
IntroductionIt may contribute to Cancer Immunol Immunother (2014) 63:1129–1140 the clearance of potentially tumourigenic cells harbouring pathogen- or danger-associated molecular patterns (PAMPs or DAMPs)
The complement system may play a dual role in the pathogenesis of cancer
No significant deviation from Hardy–Weinberg equilibrium was found for polymorphisms at codons 52 (A/D), 54 (A/B) or 57 (A/C) (p > 0.05)
Summary
It may contribute to Cancer Immunol Immunother (2014) 63:1129–1140 the clearance of potentially tumourigenic cells harbouring pathogen- or danger-associated molecular patterns (PAMPs or DAMPs). It has been suggested (based on an animal model) that myeloid-derived suppressor cells (MDSC), recruited in a C5a-dependent way, stimulate production of reactive oxygen species and reactive nitrogen species (ROS and RNS) and contribute to the inhibition of a CD8+ T cell-mediated antitumour response [1]. Mannose-Binding Lectin (MBL) may interact directly with neoplastic cells (e.g. by MBL-dependent cell-mediated cytotoxicity [2]), or inhibit metalloproteases that degrade extracellular matrix, or protect against chemotherapy-related infections or infections with cancerogenic agents (reviewed by Swierzko et al [3]). MBL may interact with antigen-presenting cells (often present in the tumour microenvironment), influence their activity/ proliferation and thereby contribute to the outcome of the anti-tumour immune response [4, 5]
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