Mannan-binding lectin (MBL) and MBL-associated serine protease-2 in children with cancer
QUESTIONS UNDER STUDY: Mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are two key components of the lectin-pathway of complement-activation. Information on the potential role of lectin-pathway components in carcinogenesis versus immune surveillance of cancer is scarce. This study aimed to determine if serum concentrations of MBL and MASP-2 differ between children with cancer and healthy age-matched controls.
METHODS: In this retrospective multicentre study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis in paediatric patients with cancer. For six diagnostic groups, these concentrations were compared with serum concentrations of age-matched healthy controls using exact Wilcoxon signed-rank tests.
RESULTS: MBL and MASP-2 were measured in serum of 372 patients. MBL was significantly higher in patients with solid tumours vs. controls (median, 2,799 vs. 1,917 μg/L; P= 0.008), and MASP-2 was significantly higher in patients with acute lymphoblastic leukaemia (406 vs. 317 μg/L; P= 0.009), Non-Hodgkin lymphoma (361 vs. 293 μg/L; P= 0.037) and CNS tumors (463 vs. 296 μg/L; P= 0.002).
CONCLUSIONS: These results may indicate a role of MBL and MASP-2 in the initiation or progression of specific paediatric cancers, while other mechanisms remain possible as well. Larger, disease-specific studies are warranted for confirmation and for elucidation of the underlying mechanisms.
- Finn OJ. Cancer immunology. N Engl J Med. 2008;358:2704–15.
- Markiewsky MM, Lambris JD. Is complement good or bad for cancer patients? A new perspective on an old dilemma. Trends Immunol. 2009;30:286–92.
- Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol. 2007;44:3875–88.
- Ytting H, Jensenius JC, Christensen IJ, Thiel S, Nielsen HJ. Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer. Scand J Gastroenterol. 2004;39:674–9.
- Baccarelli A, Hou L, Chen J, Lissowska J, El-Omar EM, Grillo P, et al. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Int J Cancer. 2006;119:1970–5.
- Swierzko AS, Florczak K, Cedzyński M, Szemraj J, Wydra D, Bak-Romaniszyn L, et al. Mannan-binding lectin (MBL) in women with tumours of the reproductive system. Cancer Immunol Immunother. 2007;56:959–71.
- Bernig T, Boersma BJ, Howe TM, Welch R, Yadavalli S, Staats B, et al. The mannose-binding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women. Carcinogenesis. 2007;28:828–36.
- Wang FY, Tahara T, Arisawa T, Shibata T, Yamashita H, Nakamura M, et al. Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Dig Dis Sci. 2008;53:2904–8.
- Ytting H, Christensen IJ, Thiel S, Jensenius JC, Nielsen HJ. Serum mannan-binding lectin-associated serine protease 2 levels in colorectal cancer: relation to recurrence and mortality. Clin Cancer Res. 2005;15:1441–6.
- Verma A, Matta A, Shukla NK, Deo SV, Gupta SD, Ralhan R. Clinical significance of mannose-binding lectin-associated serine protease-2 expression in esophageal squamous cell carcinoma. Int J Cancer. 2006;15:2930–5.
- Schmiegelow K, Garred P, Lausen B, Andreassen B, Petersen BL, Madsen HO. Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia. Blood. 2002;15:3757–60.
- Steliarova-Foucher E, Stiller CA, Lacour B, Kaatsch P. International classification of childhood cancer, third edition. Cancer. 2005;103:1457–67.
- Aittoniemi J, Miettinen A, Laippala P, Isolauri E, Viikari J, Ruuska T, Soppi E. Age-dependent variation in the serum concentration of mannan-binding protein. Acta Paediatr. 1996;85:906–9.
- Sallenbach S, Thiel S, Aebi C, Otth M, Bigler S, Jensenius JC, et al. Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2). Pediatr Allergy Immunol. (in press, DOI 10.1111/j.1399-3038.2010.01104.x)
- Ytting H, Christensen IJ, Thiel S, Jensenius JC, Svendsen MN, Nielsen L, et al. Biological variation in circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease-2 and the influence of age, gender and physical exercise. Scand J Immunol. 2007;66:458–64.
- Zehnder A, Fisch U, Hirt A, Niggli FK, Simon A, Ozsahin H, Schlapbach LJ, Ammann RA. Prognosis in pediatric hematologic malignancies is associated with serum concentration of mannose-binding lectin-associated serine protease-2 (MASP-2). Pediatr Blood Cancer. 2009;53:53–7.
- Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. Modulation of the antitumor immune response by complement. Nat Immunol. 2008;9:1225–35.
- Thiel S, Holmskov U, Hviid L, Laursen SB, Jensenius JC. The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response. Clin Exp Immunol. 1992;90:31–5.
- Herpers BL, Endeman H, de Jong BA, de Jongh BM, Grutters JC, Biesma DH, van Velzen-Blad H. Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes. Clin Exp Immunol. 2009;156:488–94.
- Schlapbach LJ, Aebi C, Otth M, Ridolfi Luethy A, Leibundgut K, Hirt A, Ammann RA. Serum levels of mannose-binding lectin and the risk of fever in neutropenic pediatric cancer patients. Pediatr Blood Cancer. 2007;49:11–6.
- Gurney JG, Bondy ML. Epidemiology of childhood cancer. In: Pizzo PA, Poplack DG, editors. Principles and practice in pediatric oncology, 5th ed. Philadelphia: Lippincott; 2006. p 1–13.