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Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation

Kormelink, Tom Groot; Powe, Desmond G.; Kuijpers, Sylvia A.; Abudukelimu, Abulikemu; Fens, Marcel H.A.M.; Pieters, Ebel H.E.; der Ven, Willemiek W. Kassing-van; Habashy, Hany O.; Ellis, Ian O.; Blokhuis, Bart R.; Thio, Marco; Hennink, Wim E.; Storm, Gert; Redegeld, Frank A.; Schiffelers, Raymond M.

Authors

Tom Groot Kormelink

Desmond G. Powe

Sylvia A. Kuijpers

Abulikemu Abudukelimu

Marcel H.A.M. Fens

Ebel H.E. Pieters

Willemiek W. Kassing-van der Ven

Hany O. Habashy

Bart R. Blokhuis

Marco Thio

Wim E. Hennink

Gert Storm

Frank A. Redegeld

Raymond M. Schiffelers



Abstract

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.

Journal Article Type Article
Publication Date May 30, 2014
Journal Oncotarget
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 5
Issue 10
Pages 3159-3167
APA6 Citation Kormelink, T. G., Powe, D. G., Kuijpers, S. A., Abudukelimu, A., Fens, M. H., Pieters, E. H., …Schiffelers, R. M. (2014). Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. Oncotarget, 5(10), 3159-3167. https://doi.org/10.18632/oncotarget.1868
DOI https://doi.org/10.18632/oncotarget.1868
Publisher URL http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=1868&path[]=2430

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