Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation
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Tom Groot Kormelink1,*, Desmond G. Powe2,*, Sylvia A. Kuijpers3, Abulikemu Abudukelimu3, Marcel H.A.M. Fens3, Ebel H.E. Pieters3, Willemiek W. Kassing-van der Ven3, Hany O. Habashy4, Ian O. Ellis5, Bart R. Blokhuis1, Marco Thio1, Wim E. Hennink3, Gert Storm3, Frank A. Redegeld1,7, and Raymond M. Schiffelers6,7
1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
2 Department of Cellular Pathology, Queen’s Medical Centre, Nottingham University Hospitals Trust, Nottingham, UK & The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
3 Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
4 Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
5 Department of Pathology, School of Molecular Medical Sciences, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK
6 Laboratory of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
7 These authors share equal senior authorship
* These authors contributed equally
Frank Redegeld, email:
Raymond Schiffelers, email:
Keywords: immunoglobulin free light chain, mast cell, biomarker, inflammation, tumor progression
Received: January 23, 2014 Accepted: March 24, 2014 Published: March 26, 2014
Inflammation is an important component of various cancers and its inflammatory cells and mediators have been shown to have prognostic potential. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. In earlier studies, we demonstrated that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen-specific manner. Increased expression of FLC was observed within stroma of various human cancers including those of breast, colon, lung, pancreas, kidney and skin, and FLC expression co-localized with areas of mast cell infiltration. In a large cohort of breast cancer patients, FLC expression was shown associated with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was found expressed in areas of inflammatory infiltration and its expression was significantly associated with poor clinical outcome. Functional importance of FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC-mediated mast cell activation strongly reduced tumor growth. Collectively, this study identifies FLCs as a ligand in the pro-tumorigenic activation of mast cells. Blocking this pathway may open new avenues for the inhibition of tumor growth, while immunohistochemical staining of FLC may be helpful in the diagnosis and prognosis of cancer.
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