Cancer Immunology, Immunotherapy

, Volume 57, Issue 9, pp 1315–1321

Impact of IFNα2b upon pSTAT3 and the MEK/ERK MAPK Pathway in Melanoma

  • Wenjun Wang
  • Howard D. Edington
  • Drazen M. Jukic
  • Uma N. M. Rao
  • Stephanie R. Land
  • John M. Kirkwood
Original Article

DOI: 10.1007/s00262-008-0466-9

Cite this article as:
Wang, W., Edington, H.D., Jukic, D.M. et al. Cancer Immunol Immunother (2008) 57: 1315. doi:10.1007/s00262-008-0466-9

Abstract

Purpose

High-dose IFNα2b (HDI) was established as the first effective adjuvant therapy for patients with high-risk resected melanoma more than a decade ago, but its fundamental molecular mechanism of action remains unclear. STAT3 and the mitogen activated protein kinases (MAPKs), especially ERK (extracellular signal-regulating kinase) and MEK (MAPK/ERK kinase), play roles in melanoma progression and host immunity. We have therefore evaluated STAT3 and MEK/ERK MAP kinases in patients with regional lymph node metastasis (stage IIIB) of melanoma in the context of a prospective neoadjuvant trial of HDI (UPCI 00-008).

Patients and methods

In the context of this trial, HDI was administered daily for 20 doses following diagnostic biopsy, and prior to definitive surgery. Immunohistochemistry for pSTAT3, phospho-MEK1/2, phospho-ERK1/2, and EGFR was performed on paired fixed (nine patients) biopsies.

Results

HDI was found to down-regulate pSTAT3 (P = 0.008) and phospho-MEK1/2 (P = 0.008) levels significantly in tumor cells. Phospho-ERK1/2 was down-regulated by HDI in tumor cells (P = 0.015), but not in lymphoid cells. HDI down-regulated EGFR (P = 0.013), but pSTAT3 activation appeared not to be associated with EGFR expression and the MEK/ERK MAPK pathway.

Conclusion

We conclude that HDI regulates MAPK signaling differentially in melanoma tumor cells and host lymphoid cells in vivo. STAT3 activation is independent of the EGFR/MEK/ERK signaling pathway.

Keywords

IFNα2b STAT3 MEK1/2 ERK1/2 Melanoma Lymph node 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Wenjun Wang
    • 1
    • 6
  • Howard D. Edington
    • 2
  • Drazen M. Jukic
    • 3
    • 4
  • Uma N. M. Rao
    • 4
  • Stephanie R. Land
    • 5
  • John M. Kirkwood
    • 1
    • 6
  1. 1.Department of Medicine, Division of Hematology/OncologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of SurgeryMagee Women’s HospitalPittsburghUSA
  3. 3.Department of DermatologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  5. 5.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  6. 6.Melanoma and Skin Cancer ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA

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