BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness

被引：38

作者：

Pelekanou, Vasiliki ^{[1
,3
,4
]}

Notas, George ^{[1
]}

Athanasouli, Paraskevi ^{[1
]}

Alexakis, Konstantinos ^{[1
]}

Kiagiadaki, Fotini ^{[1
]}

Peroulis, Nikolaos ^{[1
]}

Kalyvianaki, Konstantina ^{[1
]}

Kampouri, Errika ^{[1
]}

Polioudaki, Hara ^{[2
]}

Theodoropoulos, Panayiotis ^{[2
]}

Tsapis, Andreas ^{[1
]}

Castanas, Elias ^{[1
]}

Kampa, Marilena ^{[1
]}

机构：

[1] Univ Crete, Sch Med, Lab Expt Endocrinol, Iraklion, Greece

[2] Univ Crete, Sch Med, Dept Biochem, Iraklion, Greece

[3] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[4] Sanofi Oncol, Cambridge, MA USA

来源：

FRONTIERS IN ONCOLOGY | 2018年 / 8卷

关键词：

APRIL (TNFSF13); BAFF (TNFSF13B); BCMA (TNFRSF17); pluripotency; cancer stem cells; therapy resistance; aromatase inhibitors; androgen; TUMOR MICROENVIRONMENT; METASTASIS; PLURIPOTENCY; ANDROGENS; GROWTH; SOX2; EMT;

D O I：

10.3389/fonc.2018.00301

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells. Our findings show that both molecules increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by increasing the expression of pluripotency genes such as ALDH1A1, KLF4, and NANOG. These effects are mediated by their common receptor BCMA (TNFRSF17) and the JNK signaling pathway. Interestingly, transcriptional data analysis from breast cancer cells and patients revealed that androgens can increase APRIL transcription and subsequently, in an autocrine/paracrine manner, enhance its pluripotency effect. In conclusion, our data suggest a possible role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.

引用

页数：13

共 59 条

[1] Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey [J].