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. 2007 Jul;56(7):959-71.
doi: 10.1007/s00262-006-0250-7. Epub 2006 Nov 28.

Mannan-binding lectin (MBL) in women with tumours of the reproductive system

A St Swierzko  1 , K Florczak, M Cedzyński, J Szemraj, D Wydra, L Bak-Romaniszyn, J Emerich, Z Sułowska
Affiliations

Mannan-binding lectin (MBL) in women with tumours of the reproductive system

A St Swierzko et al. Cancer Immunol Immunother. 2007 Jul.

Abstract

Mannan-binding lectin (MBL) is an important factor of innate immunity contributing to the clearance of microorganisms. Recently, an antitumourigenic role of MBL has been suggested. We investigated mbl2 genotypes, MBL concentrations, and MBL-MASP-2 complex activity in patients with ovarian cancer. The expression of both mbl2 and masp-2 genes were investigated in ovarian tissue sections. Additionally, samples from patients with other malignant and benign tumours of the reproductive tract were tested. A significantly higher incidence of MBL deficiency/insufficiency-associated genotypes was found among patients with malignant disease compared to age-matched controls. Unexpectedly, no differences in median MBL level or MBL-MASP-2 complex activity were found between the groups. This was partly a reflection of higher MBL concentrations and MBL-MASP-2 activity in cancer patients compared with healthy women carrying corresponding genotypes. MBL-specific mRNA expression was detected in several normal and malignant ovarian tissues, as well as in ovarian epithelial cell lines. Intracellular staining with MBL-specific antibodies demonstrated the presence of MBL in ovarian cell lines, and in normal as well as malignant ovarian tissue sections. In contrast, MASP-2-specific mRNA expression was detected only in the ovary tissues of patients with malignant disease. No significant changes in MBL concentration during 3 months of chemotherapy were noticed. MBL was detected in ascites and in the fluid of benign ovarian cysts. Our findings may reflect anti-tumourigenic activity of MBL protein which might suggest potential therapeutic application. However, it cannot be excluded that mbl-2 mutant alleles may be in linkage disequilibrium with an unidentified tumour susceptibility gene(s).

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Figures

Fig. 1
Fig. 1
Comparison of serum and ascites MBL level (a) and MBL-MASP-2 complex activity (b) in patients with benign (open symbols) and malignant (filled symbols) lesion of the reproductive system. Comparison of serum and cystic fluid MBL concentrations (c)
Fig. 2
Fig. 2
a MBL concentrations in pre- and postoperatively (24–48 h after surgery) taken sera (n = 59). Median values are shown with closed circles. b Serum MBL concentrations during the course of chemotherapy. Numbers of samples tested before stages I, II, III, IV, V, and VI stage of chemotherapy equalled 34, 42, 41, 34, 34, and 20, respectively. Means shown with closed circles
Fig. 3
Fig. 3
Semi-quantitative RT–PCR of MBL (A) and MASP-2 (B) mRNA expression in ovarian tissue and cell lines. a Ovarian tissue: 1 medulla of malignant ovary; 2 cortex of malignant ovary; 3–9 tissue samples of normal ovary, mbl2 genotype: LYPA/LYPA, HYPA/LYPA, LYPA/LYPB, HYPA/LYPA, HYPA/HYPA, HYPA/HYPA and LYPA/LYPB, respectively. b Cell lines and tissue samples obtained from patients with malignancy of ovary. 1–5 Cell lines: 1 HepG2, hepatocellular carcinoma; 2 MRC-5, normal lung; 3 A549, lung carcinoma; 4 SK-OV-3, ovary carcinoma; 5 SW626, ovary carcinoma; 6–8 tissue samples of malignant ovary, mbl2 genotype: HYPA/LYPA, LYPA/LYPA and HYPA/LYPD, respectively
Fig. 4
Fig. 4
Semi-quantitative and quantitative real time RT–PCR of MBL (A) and MASP-2 (B) mRNA expression in ovarian tissue samples obtained from patients with diagnosed: a undifferentiated ovarian carcinoma; b serous carcinoma; c endometrioid carcinoma; d clear cell carcinoma; e mucinous cystadenocarcinoma; f intramural and subserosal uterine myomas. Patients’ mbl2 genotypes (in the parenthesis the grade of disease is given): 1 LYPA/LYPB, 2 LYPA/LYPB (3), 3 LYPB/LYPB (1), 4 LXPA/LYPB (1), 5 LYPA/LYPA (2), 6 HYPA/LYPB (1), 7 HYPA/LYPA (2), 8 LXPA/LYPB (2), 9 HYPA/LXPA (3), 10 HYPA/LYPA (1), 11 LXPA/LYPB (2), 12 HYPA/HYPA (2), 13 HYPA/HYPA (2), 14 HYPA/LYQA (3), 15 HYPA/LXPA (2), 16 LYQA/LYQA, 17 HYPA/LYQA
Fig. 5
Fig. 5
The intracellular presence of MBL. A Permeabilised cells of ES-2 (a) or OAW-42 (b) ovarian cancer cell lines were incubated with mouse anti-MBL mAb or mouse irrelevant IgG1, and after that, with FITC-labelled anti-mouse Ig. One of the two performed experiments with the same results is shown. B Tissue sections of normal (a) or cancerous (b) ovary stained with mouse anti-MBL mAb or rabbit anti-MBL serum, as indicated
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