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  • Oncogenomics
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Laser capture microdissection-based in vivo genomic profiling of wound keratinocytes identifies similarities and differences to squamous cell carcinoma

Oncogene volume 22, pages 3964–3976 (2003)Cite this article

Abstract

Keratinocytes undergo a dramatic phenotypic conversion during reepithelialization of skin wounds to become hyperproliferative, migratory, and invasive. This transient healing response phenotypically resembles malignant transformation of keratinocytes during squamous cell carcinoma progression. Here we present the first analysis of global changes in keratinocyte gene expression during skin wound healing in vivo, and compare these changes to changes in gene expression during malignant conversion of keratinized epithelium. Laser capture microdissection was used to isolate RNA from wound keratinocytes from incisional mouse skin wounds and adjacent normal skin keratinocytes. Changes in gene expression were determined by comparative cDNA array analyses, and the approach was validated by in situ hybridization. The analyses identified 48 candidate genes not previously associated with wound reepithelialization. Furthermore, the analyses revealed that the phenotypic resemblance of wound keratinocytes to squamous cell carcinoma is mimicked at the level of gene expression, but notable differences between the two tissue-remodeling processes were also observed. The combination of laser capture microdissection and cDNA array analysis provides a powerful new tool to unravel the complex changes in gene expression that underlie physiological and pathological remodeling of keratinized epithelium.

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Acknowledgements

We greatly acknowledge the excellent technical assistance of Lu Charboneau, the LCM Core Facility at NIH, Dr Boye Schnack-Nielsen, Pia G Knudsen & Trine Hansen, the Finsen Laboratory, Copenhagen. We thank John Post for excellent assistance with photographic reproductions. We thank Drs Henning Birkedal-Hansen and Mary Jo Danton for critically reading this manuscript. This work was supported by grants from European Commission contract QLG1-CT-2000-01131, The Danish Cancer Society, and ‘Fabrikant Vilhelm Pedersen og hustrus mindelegat’ on recommendation from The Novo Nordisk Foundation.

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  1. Proteases and Tissue Remodeling Unit, Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 211, Bethesda, 20892, MD, USA

    Tanja Xenia Pedersen, David Mitola & Thomas Henrik Bugge

  2. Finsen Laboratory, Rigshospitalet, Copenhagen, DK-2100, Denmark

    Tanja Xenia Pedersen, Leif Røge Lund, Keld Danø & Morten Johnsen

  3. Molecular Carcinogenesis Unit, Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, 20892, MD, USA

    Chidchanop Leethanakul, Vyomesh Patel & J Silvio Gutkind

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Pedersen, T., Leethanakul, C., Patel, V. et al. Laser capture microdissection-based in vivo genomic profiling of wound keratinocytes identifies similarities and differences to squamous cell carcinoma. Oncogene 22, 3964–3976 (2003). https://doi.org/10.1038/sj.onc.1206614

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