Tumor Biology

, Volume 36, Issue 4, pp 2973–2982 | Cite as

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

  • Ming Guan
  • Xiaofan Chen
  • Yingyu Ma
  • Lihua Tang
  • Lei Guan
  • Xuefeng Ren
  • Bo Yu
  • Wei Zhang
  • Bing Su
Research Article


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.


Melanoma MDA-9 GRP78 Exosomes Two-dimensional gel electrophoresis 



The study was supported, in whole or in part, by the National Natural Science Foundation of China no. 81272380 (to B.S.), no. 81272386 (to M.G.), and the Research Grants of Shenzhen Science and Technology project ZYA201106080030A and KQCX20120803145850990. The authors would like to thank Shenzhen Biomedical Research Support Platform for their excellent technical assistance.

Conflict of interest


Supplementary material

13277_2014_2930_MOESM1_ESM.doc (30 kb)
ESM 1 (DOC 30 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • 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. 1.Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Biomedical Research InstituteShenzhen Peking University - The Hong Kong University of Science and Technology Medical CenterGuangdongChina
  3. 3.Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research InstituteShenzhen Peking University - The Hong Kong University of Science and Technology Medical CenterGuangdongChina
  4. 4.Department of Pharmacology and TherapeuticsRoswell Park Cancer InstituteBuffaloUSA
  5. 5.Department of DermatologyPeking University Shenzhen HospitalShenzhenChina
  6. 6.Department of Dermatology303 Hospital of People’s Liberation Army of ChinaNanningChina
  7. 7.Skin Research Center of Guangzhou LandproofGuangzhouChina
  8. 8.Department of Epidemiology and Environmental Health, School of Public Health and Health ProfessionsThe State University of New YorkBuffaloUSA
  9. 9.Shenzhen Key Discipline of DermatologyPeking University Shenzhen HospitalShenzhenChina

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