APRIL is overexpressed in cancer: link with tumor progression.
BACKGROUND
BAFF 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.


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.
Moreaux
Jérôme
J
CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France. jerome.moreaux@inserm.fr
Veyrune
Jean-Luc
JL
De Vos
John
J
Klein
Bernard
B
D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D006493:Heparin / Q000031:analogs & derivatives / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011485:Protein Binding; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D014408:Biomarkers, Tumor; D011509:Proteoglycans; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C036090:heparin proteoglycan; D006493:Heparin; C048009:bis(3-bis(4-chlorophenyl)methyl-4-dimethylaminophenyl)amine; D004159:Diphenylamine