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

T.G. Kormelink, D.G. Powe, S.A. Kuijpers, A. Abudukelimu, M.H. Fens, E.H. Pieters, W.W. Kassing-Van der Ven, H.O. Habashy, I.O. Ellis, B.R. Blokhuis, M. Thio, W.E. Hennink, Gerrit Storm, F.A. Redegeld, R.M. Schiffelers

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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.
Original languageUndefined
Pages (from-to)3159-3167
JournalOncotarget
Volume5
Issue number10
Publication statusPublished - 2014

Keywords

  • METIS-309160
  • IR-95135

Cite this

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.
Kormelink, T.G. ; Powe, D.G. ; Kuijpers, S.A. ; Abudukelimu, A. ; Fens, M.H. ; Pieters, E.H. ; Kassing-Van der Ven, W.W. ; Habashy, H.O. ; Ellis, I.O. ; Blokhuis, B.R. ; Thio, M. ; Hennink, W.E. ; Storm, Gerrit ; Redegeld, F.A. ; Schiffelers, R.M. / Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. In: Oncotarget. 2014 ; Vol. 5, No. 10. pp. 3159-3167.
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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.",
keywords = "METIS-309160, IR-95135",
author = "T.G. Kormelink and D.G. Powe and S.A. Kuijpers and A. Abudukelimu and M.H. Fens and E.H. Pieters and {Kassing-Van der Ven}, W.W. and H.O. Habashy and I.O. Ellis and B.R. Blokhuis and M. Thio and W.E. Hennink and Gerrit Storm and F.A. Redegeld and R.M. Schiffelers",
note = "Oncotarget - ISSN: 19492553",
year = "2014",
language = "Undefined",
volume = "5",
pages = "3159--3167",
journal = "Oncotarget",
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Kormelink, TG, Powe, DG, Kuijpers, SA, Abudukelimu, A, Fens, MH, Pieters, EH, Kassing-Van der Ven, WW, Habashy, HO, Ellis, IO, Blokhuis, BR, Thio, M, Hennink, WE, Storm, G, Redegeld, FA & Schiffelers, RM 2014, 'Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation' Oncotarget, vol. 5, no. 10, pp. 3159-3167.

Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. / Kormelink, T.G.; Powe, D.G.; Kuijpers, S.A.; Abudukelimu, A.; Fens, M.H.; Pieters, E.H.; Kassing-Van der Ven, W.W.; Habashy, H.O.; Ellis, I.O.; Blokhuis, B.R.; Thio, M.; Hennink, W.E.; Storm, Gerrit; Redegeld, F.A.; Schiffelers, R.M.

In: Oncotarget, Vol. 5, No. 10, 2014, p. 3159-3167.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation

AU - Kormelink, T.G.

AU - Powe, D.G.

AU - Kuijpers, S.A.

AU - Abudukelimu, A.

AU - Fens, M.H.

AU - Pieters, E.H.

AU - Kassing-Van der Ven, W.W.

AU - Habashy, H.O.

AU - Ellis, I.O.

AU - Blokhuis, B.R.

AU - Thio, M.

AU - Hennink, W.E.

AU - Storm, Gerrit

AU - Redegeld, F.A.

AU - Schiffelers, R.M.

N1 - Oncotarget - ISSN: 19492553

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - METIS-309160

KW - IR-95135

M3 - Article

VL - 5

SP - 3159

EP - 3167

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 10

ER -