Limits...
APRIL is overexpressed in cancer: link with tumor progression.

Moreaux J, Veyrune JL, De Vos J, Klein B - BMC Cancer (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France. jerome.moreaux@inserm.fr

ABSTRACT

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.

Conclusion: Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.

Show MeSH

Related in: MedlinePlus

BAFF expression in various cancers. BAFF gene expression in normal brain, glioblastoma multiforme [34-37], normal breast, breast carcinoma[40], normal esophagus, esophageal adenocarcinoma[41], normal kidney, renal carcinoma[42], normal testis, adult male germ cell tumor[43], Hodgkin lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma[33]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2662875&req=5

Figure 1: BAFF expression in various cancers. BAFF gene expression in normal brain, glioblastoma multiforme [34-37], normal breast, breast carcinoma[40], normal esophagus, esophageal adenocarcinoma[41], normal kidney, renal carcinoma[42], normal testis, adult male germ cell tumor[43], Hodgkin lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma[33]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.

Mentions: 40 tumor types were investigated, including 36 solid tumors and 4 hematological tumors (Additional file 1: Table 1). BAFF gene is overexpressed in 1/4 hematological tumors and in 5/36 solid tumors. BAFF is overexpressed in Hodgkin lymhoma compared to normal B cells (P = 4.9E-11), 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]. Four independent studies have shown BAFF overexpression in glioblastoma compared to normal brain (P = 5.4E-13, P = 8E-6, P = 5.3E-5 and P = 0.008) [34-37] (Figure 1). Following stimulation with inflammatory cytokines, astrocytes in vitro produce high amounts of BAFF. BAFF is expressed in astrocytes in the normal human central nervous system and is strongly upregulated in activated astrocytes in the demyelinated lesions of multiple sclerosis[38]. BAFF secretion could be relevant in sustaining intrathecal B cell responses in autoimmune and infectious diseases of the central nervous system. Accordingly, BAFF expression is readily induced in the central nervous system by neurotrophic viruses and correlates with the recruitment of antibody-secreting cells[39]. The overexpression of BAFF in brain tumors could be linked to the accumulation of tumor cells or to inflammatory signals. Regarding other cancers, 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 = 3.7E-4), 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).


APRIL is overexpressed in cancer: link with tumor progression.

Moreaux J, Veyrune JL, De Vos J, Klein B - BMC Cancer (2009)

BAFF expression in various cancers. BAFF gene expression in normal brain, glioblastoma multiforme [34-37], normal breast, breast carcinoma[40], normal esophagus, esophageal adenocarcinoma[41], normal kidney, renal carcinoma[42], normal testis, adult male germ cell tumor[43], Hodgkin lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma[33]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662875&req=5

Figure 1: BAFF expression in various cancers. BAFF gene expression in normal brain, glioblastoma multiforme [34-37], normal breast, breast carcinoma[40], normal esophagus, esophageal adenocarcinoma[41], normal kidney, renal carcinoma[42], normal testis, adult male germ cell tumor[43], Hodgkin lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma and follicular lymphoma[33]. Data sets in a single panel were from the same study. GEP data are log transformed and normalized as previously described[32]. In brackets, are indicated the number of normal or tumor samples.
Mentions: 40 tumor types were investigated, including 36 solid tumors and 4 hematological tumors (Additional file 1: Table 1). BAFF gene is overexpressed in 1/4 hematological tumors and in 5/36 solid tumors. BAFF is overexpressed in Hodgkin lymhoma compared to normal B cells (P = 4.9E-11), 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]. Four independent studies have shown BAFF overexpression in glioblastoma compared to normal brain (P = 5.4E-13, P = 8E-6, P = 5.3E-5 and P = 0.008) [34-37] (Figure 1). Following stimulation with inflammatory cytokines, astrocytes in vitro produce high amounts of BAFF. BAFF is expressed in astrocytes in the normal human central nervous system and is strongly upregulated in activated astrocytes in the demyelinated lesions of multiple sclerosis[38]. BAFF secretion could be relevant in sustaining intrathecal B cell responses in autoimmune and infectious diseases of the central nervous system. Accordingly, BAFF expression is readily induced in the central nervous system by neurotrophic viruses and correlates with the recruitment of antibody-secreting cells[39]. The overexpression of BAFF in brain tumors could be linked to the accumulation of tumor cells or to inflammatory signals. Regarding other cancers, 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 = 3.7E-4), 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).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France. jerome.moreaux@inserm.fr

ABSTRACT

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.

Conclusion: Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.

Show MeSH
Related in: MedlinePlus