HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells

被引:136
作者
Ono, Kisho [1 ,2 ]
Eguchi, Takanori [1 ,3 ]
Sogawa, Chiharu [1 ]
Calderwood, Stuart K. [4 ]
Futagawa, Junya [5 ]
Kasai, Tomonari [6 ]
Seno, Masaharu [6 ]
Okamoto, Kuniaki [1 ]
Sasaki, Akira [2 ]
Kozaki, Ken-ichi [1 ]
机构
[1] Grad Sch Med Dent & Pharmaceut Sci, Dept Dent Pharmacol, Okayama, Japan
[2] Grad Sch Med Dent & Pharmaceut Sci, Dept Oral & Maxillofacial Surg, Okayama, Japan
[3] Okayama Univ, Adv Res Ctr Oral & Craniofacial Sci, Grad Sch Med Dent & Pharmaceut Sci, Dent Sch, Okayama, Japan
[4] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA
[5] Mitsui Knowledge Ind, Dept Biomed Solut Ctr, Tokyo, Japan
[6] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn, Okayama, Japan
基金
日本学术振兴会;
关键词
EV proteomics; exosome; extracellular vesicle; heat shock proteins; lymph-node-metastatic oral cancer; molecular chaperone; HEAT-SHOCK PROTEINS; EXOSOMAL PROTEINS; MICROVESICLES; SECRETION; MECHANISM; EXOCARTA; RNA;
D O I
10.1002/jcb.27039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Cancer cells often secrete extracellular vesicles (EVs) that carry heat shock proteins (HSPs) with roles in tumor progression. Oral squamous cell carcinoma (OSCC) belongs to head and neck cancers (HNC) whose lymph-node-metastases often lead to poor prognosis. We have examined the EV proteome of OSCC cells and found abundant secretion of HSP90-enriched EVs in lymph-node-metastatic OSCC cells. Double knockdown of HSP90 and HSP90, using small interfering RNA significantly reduced the survival of the metastatic OSCC cells, although single knockdown of each HSP90 was ineffective. Elevated expression of these HSP90 family members was found to correlate with poor prognosis of HNC cases. Thus, elevated HSP90 levels in secreted vesicles are potential prognostic biomarkers and therapeutic targets in metastatic OSCC.
引用
收藏
页码:7350 / 7362
页数:13
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