APRIL is overexpressed in cancer: link with tumor progression

Jérôme Moreaux,Jean-Luc Veyrune,John De Vos,Bernard Klein

doi:10.1186/1471-2407-9-83

Jérôme Moreaux, Jean-Luc Veyrune + Show 2 more

Open Access

https://doi.org/10.1186/1471-2407-9-83

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Abstract

BackgroundBAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.MethodsWe compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.ResultsWe found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.ConclusionTaken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.

Highlights

BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF receptor (BAFF-R)
BAFF is overexpressed in Hodgkin lymhoma compared to normal B cells (P = 4.9E11), in Burkitt lymphoma compared to normal B cells (P = 5.4E-5), in diffuse large B cell lymphoma compared to normal B cells (P = .01) and in follicular lymphoma compared to normal B cells (P = 2E-6)[33]
BAFF was found significantly overexpressed in breast carcinoma compared to normal breast (Richardson et al[40]; P = 2.4E-7), in esophageal adenocarcinoma compared to normal esophagus (Hao et al[41]; P = 3.7E4), in clear cell renal cell carcinoma compared to normal kidney (Lenburg et al[42]; P = 2.1E-5) and in adult male germ cell tumor compared to normal testis (Korkola et al[43]; P = 8.3E-18)

Summary

Introduction

BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. APRIL and BAFF are two members of the TNF family. BAFF is a type II transmembrane protein that can be secreted after proteolytical cleavage from the cell membrane[1,2]. APRIL can be expressed as a cell surface fusion protein with TWEAK called TWE-PRIL[4,5]. Both ligands bind to TACI (transmembrane activator and CAML interactor) and BCMA (Bcell maturation antigen), two members of the TNFR family.

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