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.
Highlights
Inflammation is considered a critical component of tumor progression in some cancer types [1]
The cellular localization of kappa and lambda free light chains (FLC) protein expression was investigated in tissue microarrays www.impactjournals.com/oncotarget (TMA) comprising human cancer specimens derived from breast, pancreas, lung, colon, skin, and kidney
FLC protein expression was detected in tumor-associated tissue from human breast, pancreas, lung, colon, skin and kidney, while FLC staining was virtually absent in comparative healthy tissue
Summary
Inflammation is considered a critical component of tumor progression in some cancer types [1]. Other studies indicate that the number of mast cells correlates with an increase in intra-tumoral microvessel density, enhanced tumor growth and invasion, and poor clinical outcome [6, 10,11,12]. Mast cells can recruit other inflammatory cells including macrophages that are implicated in promoting cancer invasion and metastasis [13, 14]. These findings are supported by recent studies in various experimental tumor models that demonstrate an essential role for mast cells in tumor expansion [10, 15,16,17]
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