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Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1α-directed invasion of human basal cell carcinoma cells

Oncogene volume 26, pages 2491–2501 (2007)Cite this article

Abstract

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans and is usually characterized by local aggressiveness with little metastatic potential, although deep invasion, recurrence, and regional and distant metastases may occur. Here, we studied the mechanism of BCC invasion. We found that human BCC tissues and a BCC cell line had significant expression of CXCR4, which was higher in invasive than non-invasive BCC types. Further, of 19 recurrent tumors among 390 BCCs diagnosed during the past 12 years, 17/19 (89.5%) had high CXCR4 expression. We found that the CXCR4 ligand, stromal-cell-derived factor 1α (SDF-1α), directed BCC invasion and that this was mediated by time-dependent upregulation of mRNA expression and gelatinase activity of matrix metalloproteinase-13 (MMP-13). The transcriptional regulation of MMP-13 by SDF-1α was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the AP-1 component c-Jun. Finally, CXCR4-transfected BCC cells injected into nude mice induced aggressive BCCs that co-expressed CXCR4 and MMP-13. The identification of SDF-1α/CXCR4 as an important factor in BCC invasiveness may contribute insight into mechanisms involved in the aggressive potential of human BCC and may improve therapy for invasive BCCs.

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Acknowledgements

We thank Dr Din-Lii Lin from TaiGen Biotechnology Company (Taipei, Taiwan) for providing pCMV-CXCR4 and AMD 3100. This work was supported by grants to S-H Jee from the National Science Council of Taiwan (NSC 93-2314-B-002-072, NSC 95-2314-B-002-001) and to C-Y Chu from National Taiwan University Hospital (NTUH 93N016, NTUH 94N027, NTUH 95M06) and the National Science Council of Taiwan (NSC 95-2314-B-002-129).

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  1. S-H Jee and M-L Kuo: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    C-Y Chu & S-H Jee

  2. Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology, College of Medicine and Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan

    C-Y Chu, S-T Cha, C-C Chang, Y-C Lu & M-L Kuo

  3. Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    C-H Hsiao

  4. Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    C-T Tan & Y-C Lu

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Correspondence to M-L Kuo.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Chu, CY., Cha, ST., Chang, CC. et al. Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1α-directed invasion of human basal cell carcinoma cells. Oncogene 26, 2491–2501 (2007). https://doi.org/10.1038/sj.onc.1210040

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