MDA-9 and GRP78 as potential diagnostic biomarkers for early detection of melanoma metastasis

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• 作者：Ming Guan ; Xiaofan Chen ; Yingyu Ma ; Lihua Tang ; Lei Guan ; Xuefeng Ren…
• 关键词：Melanoma ; MDA ; 9 ; GRP78 ; Exosomes ; Two ; dimensional gel electrophoresis
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：36
• 期：4
• 页码：2973-2982
• 全文大小：3,796 KB
• 参考文献：1.Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol. 2002;146 Suppl 61:1-.View Article PubMed
  2.Little EG, Eide MJ. Update on the current state of melanoma incidence. Dermatol Clin. 2012;30:355-1.View Article PubMed
  3.Balch CM, Sober AJ, Soong SJ, Gershenwald JE, Committee AMS. The new melanoma staging system. Semin Cutan Med Surg. 2003;22:42-4.View Article PubMed
  4.Berger MF, Levin JZ, Vijayendran K, Sivachenko A, Adiconis X, Maguire J, et al. Integrative analysis of the melanoma transcriptome. Genome Res. 2010;20:413-7.View Article PubMed Central PubMed
  5.Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nat. 2010;463:191-.View Article
  6.Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on t lymphocytes. Cancer Res. 2006;66:9290-.View Article PubMed
  7.Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360:295-05.View Article PubMed
  8.Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 1820;2012:940-.
  9.Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, et al. Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PLoS One. 2012;7:e46874.View Article PubMed Central PubMed
  10.Nicholas J. A new diagnostic tool with the potential to predict tumor metastasis. J Natl Cancer Inst. 2013;105:371-.View Article PubMed
  11.Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport rna and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470-.View Article PubMed Central PubMed
  12.Skokos D, Botros HG, Demeure C, Morin J, Peronet R, Birkenmeier G, et al. Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol. 2003;170:3037-5.View Article PubMed
  13.Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998;273:20121-.View Article PubMed
  14.Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem. 2003;278:10963-2.View Article PubMed
  15.Nakayama T, Taback B, Turner R, Morton DL, Hoon DS. Molecular clonality of in-transit melanoma metastasis. Am J Pathol. 2001;158:1371-.View Article PubMed Central PubMed
  16.Daigo Y, Chin SF, Gorringe KL, Bobrow LG, Ponder BA, Pharoah PD, et al. Degenerate oligonucleotide primed-polymerase chain reaction-based array comparative genomic hybridization for extensive amplicon profiling of breast cancers: a new approach for the molecular analysis of paraffin-embedded cancer tissue. Am J Pathol. 2001;158:1623-1.View Article PubMed Central PubMed
  17.Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through met. Nat Med. 2012;18:883-1.View Article PubMed Central PubMed
  18.Su B, Bu Y, Engelberg D, Gelman IH. Ssecks/gravin/akap12 inhibits cancer cell invasiveness and chemotaxis by suppressing a protein kinase C- Raf/MEK/ERK pathway. J Biol Chem. 2010;285:4578-6.View Article PubMed Central PubMed
  19.Hwangbo C, Kim J, Lee JJ, Lee JH. Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase calpha and the pdz adapter protein mda-9/syntenin. Cancer Res. 2010;70:1645-5.View Article PubMed
  20.Boukerche H, Su ZZ, Prevot C, Sarkar D, Fisher PB. Mda-9/syntenin promotes metastasis in human melanoma cells by activating c-src. Proc Natl Acad Sci U S A. 2008;105:15914-.View Article PubMed Central PubMed
  21.Papalas JA, Vollmer RT, Gonzalez-Gronow M, Pizzo SV, Burchette J, Youens KE, et al. Patterns of grp78 and mtj1 expression in primary cutaneous malignant melanoma. Mod Pathol: Off J U S Can Acad Pathol Inc. 2010;23:134-3.View Article
  22.Zhuang L, Scolyer RA, Lee CS, McCarthy SW, Cooper WA, Zhang XD, et al. Expression of glucose-regulated stress protein grp78 is related to progression of melanoma. Histopathol. 2009;54:462-0.View Article
  23.Selim MA, Burchette JL, Bowers EV, de Ridder GG, Mo L, Pizzo SV, et al. Changes in oligosacch
• 作者单位：Ming Guan (1)
  Xiaofan Chen (2) (3)
  Yingyu Ma (4)
  Lihua Tang (5) (6)
  Lei Guan (7)
  Xuefeng Ren (8)
  Bo Yu (3) (5) (9)
  Wei Zhang (2) (3) (9)
  Bing Su (2) (3) (8) (9)
  
  1. Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China
  2. Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Guangdong, 518036, China
  3. Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Guangdong, 518036, China
  4. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA
  5. Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China
  6. Department of Dermatology, 303 Hospital of People’s Liberation Army of China, Nanning, Guangxi Zhuang Autonomous Region, 530021, China
  7. Skin Research Center of Guangzhou Landproof, Guangzhou, Guangdong, 510630, China
  8. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY, 14214, USA
  9. Shenzhen Key Discipline of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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 (α-enolase, cofilin-1, LDH, m-β-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.