Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis for primary effusion lymphoma

被引：52

作者：

Dai, Lu ^{[1
,2
,3
,4
]}

Trillo-Tinoco, Jimena ^{[5
]}

Cao, Yueyu ^{[2
,3
]}

Bonstaff, Karlie ^{[4
]}

Doyle, Lisa ^{[4
]}

Del Valle, Luis ^{[5
]}

Whitby, Denise ^{[6
]}

Parsons, Chris ^{[4
]}

Reiss, Krzysztof ^{[4
]}

Zabaleta, Jovanny ^{[7
]}

Qin, Zhiqiang ^{[1
,2
,3
]}

机构：

[1] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA

[2] Tongji Univ, East Hosp, Sch Med, Res Ctr Translat Med, Shanghai 200092, Peoples R China

[3] Tongji Univ, East Hosp, Sch Med, Key Lab Arrhythmias, Shanghai 200092, Peoples R China

[4] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Med, New Orleans, LA USA

[5] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Pathol, New Orleans, LA USA

[6] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD USA

[7] Louisiana State Univ, Hlth Sci Ctr, Louisiana Canc Res Ctr, Dept Pediat, New Orleans, LA USA

来源：

BLOOD | 2015年 / 126卷 / 26期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

SARCOMA-ASSOCIATED HERPESVIRUS; HEPATOCYTE GROWTH-FACTOR; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; RECEPTOR TYROSINE KINASE; C-MET; SIGNALING PATHWAYS; NSC NUMBER-663249; SOMATIC MUTATIONS; TUMOR-REGRESSION; SOLID LYMPHOMAS;

D O I：

10.1182/blood-2015-07-658823

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo. The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model. By using microarray analysis, we identify many novel genes that are potentially controlled by HGF/c-MET within PEL cells. One of the downstream candidates, ribonucleoside-diphosphate reductase subunit M2 (RRM2), also displays the promising therapeutic value for PEL treatment. Our findings provide the framework for development of HGF/c-MET-focused therapy and implementation of clinical trials for PEL patients.

引用

页码：2821 / 2831

页数：11

共 56 条

[1] Intracellular Kaposi's sarcoma-associated herpesvirus load determines early loss of immune synapse components [J].