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学科主题: 临床医学
题名:
MDA-9 and GRP78 as potential diagnostic biomarkers for early detection of melanoma metastasis
作者: Guan, Ming1; Chen, Xiaofan2,3; Ma, Yingyu4; Tang, Lihua5,6; Guan, Lei7; Ren, Xuefeng8; Yu, Bo3,5,9; Zhang, Wei2,3,9; Su, Bing2,3,8,9
关键词: Melanoma ; MDA-9 ; GRP78 ; Exosomes ; Two-dimensional gel electrophoresis
刊名: TUMOR BIOLOGY
发表日期: 2015-04-01
DOI: 10.1007/s13277-014-2930-9
卷: 36, 期:4, 页:2973-2982
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: CELL-DERIVED EXOSOMES ; PROTEIN GRP78 ; CANCER-CELLS ; MDA-9/SYNTENIN ; GROWTH ; LYMPHOCYTES ; PROGRESSION ; ACTIVATION ; EXPRESSION ; SURVIVAL
英文摘要:

Metastatic melanoma, the primary cause of skin cancer-related death, warrants new diagnostic and therapeutic approaches that target the regulatory machinery at molecular level. The heterogeneity and complexity of melanoma result in the difficulty to find biomarkers and targets for early detection and treatment. Here, we investigated metastasis-associated proteins by comparing the proteomic profiles of primary cutaneous melanomas to their matched lymph node metastases, which minimizes heterogeneity among samples from different patients. Results of two-dimensional gel electrophoresis (2-DE) followed by proteomic analysis revealed eight differentially expressed proteins. Among them, seven proteins (alpha-enolase, cofilin-1, LDH, m-beta-actin, Nm23, GRP78, and MDA-9) showed increased and one (annexin A2) showed decreased expression in metastatic lymph node tissues than in primary melanomas. MDA-9 and GRP78 were the most highly expressed proteins in lymph node metastases, which was validated by immunohistochemical staining. Moreover, exosomes from serum samples of metastatic melanoma patients contained higher levels of MDA-9 and GRP78 than those of patients without metastases, indicating the potential of MDA-9 and GRP78 to be biomarkers for early detection of metastasis. Further, small interfering RNA (siRNA)-mediated knockdown confirmed a functional role for MDA-9 and GRP78 to promote cell invasion in the A375 cells. Finally, we showed that GRP78 co-localized with MDA-9 in 293T cells. Taken together, our findings support MDA-9, co-expressed with GRP78, as a melanoma protein associated with lymph node metastasis. Investigating how MDA-9 and GRP78 interact to contribute to melanoma metastasis and disease progression could reveal new potential avenues of targeted therapy and/or useful biomarkers for diagnosis and prognosis.

语种: 英语
所属项目编号: 81272380 ; 81272386 ; ZYA201106080030A ; KQCX20120803145850990
项目资助者: National Natural Science Foundation of China ; Research Grants of Shenzhen Science and Technology
WOS记录号: WOS:000352885900087
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65629
Appears in Collections:北京大学深圳医院_皮肤性病科_期刊论文

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作者单位: 1.Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA
2.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Lab Med, Shanghai 200040, Peoples R China
3.Shenzhen Peking Univ, Biomed Res Inst, Shenzhen 518036, Guangdong, Peoples R China
4.Shenzhen Peking Univ, Biomed Res Inst, Shenzhen Key Lab Translat Med Dermatol, Shenzhen 518036, Guangdong, Peoples R China
5.Peking Univ, Shenzhen Hosp, Dept Dermatol, Shenzhen 518036, Guangdong, Peoples R China
6.Peoples Liberat Army, Hosp 303, Dept Dermatol, Nanning 530021, Guangxi Zhuang, Peoples R China
7.Skin Res Ctr Guangzhou Landproof, Guangzhou 510630, Guangdong, Peoples R China
8.SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA
9.Peking Univ, Shenzhen Hosp, Shenzhen Key Discipline Dermatol, Shenzhen 518036, Guangdong, Peoples R China

Recommended Citation:
Guan, Ming,Chen, Xiaofan,Ma, Yingyu,et al. MDA-9 and GRP78 as potential diagnostic biomarkers for early detection of melanoma metastasis[J]. TUMOR BIOLOGY,2015,36(4):2973-2982.
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