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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.

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Related in: MedlinePlus

TACI expression in various cancers. TACI gene expression in normal plasma cells, smoldering myeloma[60], normal thyroid, thyroid carcinoma[61] and lymphoma[62]. 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.
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Figure 4: TACI expression in various cancers. TACI gene expression in normal plasma cells, smoldering myeloma[60], normal thyroid, thyroid carcinoma[61] and lymphoma[62]. 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: We have previously reported the relevance of Affymetrix microarrays to quantify BCMA and TACI expressions in MM since microarray data were validated by real time RT-PCR and flow cytometry[20,21,59]. No differences in BCMA or BAFF-R expression between tumor cells and their normal counterparts could be found in the 40 cancer types available from Oncomine database. By contrast, a significant TACI overexpression was found in smoldering myeloma compared to normal plasma cells (Zhan et al[60]; P = 0.0009) and in thyroid carcinomas compared to normal thyroid (Huang et al[61]; P = 0.005) (Figure 4). Interestingly, we found that TACI expression is associated with a poor prognosis in Burkitt lymphoma. TACI is significantly overexpressed in patients presenting Burkitt lymphoma who were dead at five years compared to patients alive at five years (Dave et al[62]; P = 0.004) (Figure 4). Recently, it was described that APRIL-TACI interactions mediate non-Hodgkin lymphoma B-cell proliferation through Akt, regulating cyclin D1 and P21 expression[63]. These data suggest that TACI is the main receptor for BAFF/APRIL in lymphoma cells and is associated with a bad prognosis. TACI therefore represents a potential lymphoma therapeutic target.


APRIL is overexpressed in cancer: link with tumor progression.

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

TACI expression in various cancers. TACI gene expression in normal plasma cells, smoldering myeloma[60], normal thyroid, thyroid carcinoma[61] and lymphoma[62]. 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 4: TACI expression in various cancers. TACI gene expression in normal plasma cells, smoldering myeloma[60], normal thyroid, thyroid carcinoma[61] and lymphoma[62]. 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: We have previously reported the relevance of Affymetrix microarrays to quantify BCMA and TACI expressions in MM since microarray data were validated by real time RT-PCR and flow cytometry[20,21,59]. No differences in BCMA or BAFF-R expression between tumor cells and their normal counterparts could be found in the 40 cancer types available from Oncomine database. By contrast, a significant TACI overexpression was found in smoldering myeloma compared to normal plasma cells (Zhan et al[60]; P = 0.0009) and in thyroid carcinomas compared to normal thyroid (Huang et al[61]; P = 0.005) (Figure 4). Interestingly, we found that TACI expression is associated with a poor prognosis in Burkitt lymphoma. TACI is significantly overexpressed in patients presenting Burkitt lymphoma who were dead at five years compared to patients alive at five years (Dave et al[62]; P = 0.004) (Figure 4). Recently, it was described that APRIL-TACI interactions mediate non-Hodgkin lymphoma B-cell proliferation through Akt, regulating cyclin D1 and P21 expression[63]. These data suggest that TACI is the main receptor for BAFF/APRIL in lymphoma cells and is associated with a bad prognosis. TACI therefore represents a potential lymphoma therapeutic target.

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