Moreaux Jérôme, Veyrune Jean-Luc, De Vos John, Klein Bernard
CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France.
BMC Cancer. 2009 Mar 16;9:83. doi: 10.1186/1471-2407-9-83.
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.
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.
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.
Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.
BAFF和APRIL共享两种受体——TACI和BCMA，并且BAFF可与第三种受体BAFF-R结合。在血液系统恶性肿瘤中，BAFF和APRIL的表达增加。BAFF和APRIL对于正常和恶性B淋巴细胞的存活至关重要，并且在包括B细胞非霍奇金淋巴瘤、慢性淋巴细胞白血病、霍奇金淋巴瘤、多发性骨髓瘤和华氏巨球蛋白血症在内的各种B细胞恶性肿瘤中，均已报道BAFF或APRIL及其受体（BCMA、TACI或BAFF-R）的表达发生改变。
我们使用公开可用的基因表达数据，包括Oncomine癌症微阵列数据库，比较了40种人类肿瘤类型（脑、上皮、淋巴、生殖细胞）中BAFF、APRIL、TACI和BAFF-R基因表达与其正常组织对应物的基因表达。
我们发现TACI在多发性骨髓瘤和甲状腺癌中显著过表达，并且TACI表达与淋巴瘤的预后相关。此外，BAFF和APRIL在许多癌症中过表达，并且我们表明APRIL表达与肿瘤进展相关。我们还发现在APRIL过表达或为预后因素的肿瘤中，至少有一种带有硫酸乙酰肝素链（HS）的蛋白聚糖过表达，而HS是APRIL和TACI的共受体。APRIL可直接通过HS蛋白聚糖诱导存活或增殖。
综上所述，这些数据表明APRIL是多种恶性肿瘤的潜在预后因素。
