title: Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation.
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.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Groot Kormelink
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Powe
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Kuijpers
authors.forename: Abulikemu
authors.initials: A
authors.lastname: Abudukelimu
authors.forename: Marcel H A M
authors.initials: MH
authors.lastname: Fens
authors.forename: Ebel H E
authors.initials: EH
authors.lastname: Pieters
authors.forename: Willemiek W
authors.initials: WW
authors.lastname: Kassing van der Ven
authors.forename: Hany O
authors.initials: HO
authors.lastname: Habashy
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Bart R
authors.initials: BR
authors.lastname: Blokhuis
authors.forename: Marco
authors.initials: M
authors.lastname: Thio
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Frank A
authors.initials: FA
authors.lastname: Redegeld
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D015550:Cell Degranulation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D008407:Mast Cells / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009374:Neoplasms, Experimental; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D007147:Immunoglobulin Light Chains