Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression

被引：126

作者：

Hao, Mu ^{[1
,2
,3
]}

Zhang, Li ^{[4
]}

An, Gang ^{[1
,2
,3
]}

Meng, Hengxing ^{[5
]}

Han, Youjin ^{[1
,2
,3
]}

Xie, Zhenqing ^{[1
,2
,3
]}

Xu, Yan ^{[1
,2
,3
]}

Li, Changhong ^{[1
,2
,3
]}

Yu, Zhen ^{[1
,2
,3
]}

Chang, Hong ^{[6
]}

Qiu, Lugui ^{[1
,2
,3
,5
]}

机构：

[1] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China

[2] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China

[3] Peking Union Med Coll, Tianjin, Peoples R China

[4] Sichuan Univ, W China Hosp, Blood Sect, Chengdu 610064, Sichuan, Peoples R China

[5] Umbil Cord Blood Bank Tianjin, Tianjin, Peoples R China

[6] Univ Toronto, Univ Hlth Network, Dept Lab Hematol, Toronto, ON M5S 1A1, Canada

来源：

LEUKEMIA & LYMPHOMA | 2011年 / 52卷 / 09期

基金：

中国国家自然科学基金;

关键词：

Multiple myeloma; stromal cells; apoptosis; drug resistance; miRNA-15a; MULTIPLE-MYELOMA; PROTEASOME INHIBITORS; DRUG-RESISTANCE; TUMOR; VEGF; TARGETS; MICROENVIRONMENT; THERAPY; FOCUS;

D O I：

10.3109/10428194.2011.576791

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Despite unsurpassed anti-tumor activity of bortezomib for multiple myeloma (MM), drug resistance has emerged as a challenge, especially when MM cells adhere to the stroma. This study aimed to determine whether bone marrow stromal cells (BMSCs) have a role in the development of chemoresistance in MM. Our data demonstrate that the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and cell-to-cell contact with microenvironment-derived stromal cells from patients with multiple myeloma (MM-BMSCs) significantly decreased the sensitivity of myeloma cells to bortezomib treatment. Mechanistically, we found that microRNA (miRNA)-15a expression was up-regulated in U266 and NCI-H929 cells treated by bortezomib, which was inhibited by MM-BMSCs. miRNA-15a transfected myeloma cells were arrested in G1/S checkpoint and secreted less VEGF compared to control transfected cells, although no significant difference was found in VEGF mRNA levels. In conclusion, our data suggest that via suppressing miRNA-15a expression, BMSCs provide survival support and protect myeloma cells from bortezomib induced apoptosis.

引用

页码：1787 / 1794

页数：8

共 24 条

[1]

Targeted therapy of multiple myeloma based upon tumor-microenvironmental interactions [J].