Ann Dermatol.  2014 Jun;26(3):363-373.

The Effect of Imiquimod on Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Malignant Melanoma Cell Invasion

Affiliations
  • 1Yeouido Oracle Dermatology and Cosmetic Dermatosurgery Clinic, Seoul, Korea.
  • 2Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. kychung@yuhs.ac
  • 3Department of Dermatology, Myongji Hospital, Kwandong University College of Medicine, Goyang, Korea.

Abstract

BACKGROUND
A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
OBJECTIVE
To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs.
METHODS
Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting.
RESULTS
Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration-dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels.
CONCLUSION
Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating MMPs and TIMPs.

Keyword

Imiquimod; Invasion; Melanoma; Matrix metalloproteinase; Tissue inhibitor of metalloproteinase
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