Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation
| Autor: | Kormelink, Tom Groot, Powe, Desmond G., Kuijpers, Sylvia A., Abudukelimu, Abulikemu, Fens, Marcel H A M, Pieters, Ebel H E, Kassing-Van der Ven, Willemiek W., Habashy, Hany O., Ellis, Ian O., Blokhuis, Bart R., Thio, Marco, Hennink, Wim E., Storm, Gert, Redegeld, Frank A., Schiffelers, Raymond M., UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmacology, Pharmaceutics, Sub Immunopharmacology, Sub Drug targeting, Sub Drug delivery, Sub General Pharmaceutics |
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| Přispěvatelé: | UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmacology, Pharmaceutics, Sub Immunopharmacology, Sub Drug targeting, Sub Drug delivery, Sub General Pharmaceutics |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Angiogenesis Inflammation Breast Neoplasms Kaplan-Meier Estimate Cell Degranulation Mast cell Mice Breast cancer Stroma hemic and lymphatic diseases medicine Biomarkers Tumor Animals Humans Mast Cells Melanoma Immunoglobulin free light chain Aged Proportional Hazards Models biology Neoplasms Experimental Biomarker Middle Aged medicine.disease Prognosis Immunohistochemistry Tumor progression Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Oncology Tissue Array Analysis biology.protein Female Immunoglobulin Light Chains Antibody medicine.symptom Research Paper |
| Zdroj: | Oncotarget, 5(10), 3159. Impact Journals LLC Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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