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Archives of Dermatological Research

, Volume 306, Issue 5, pp 489–496 | Cite as

Clinicopathological roles of S100A8 and S100A9 in cutaneous squamous cell carcinoma in vivo and in vitro

  • Dae-Kyoung Choi
  • Zheng Jun Li
  • In-Kyu Chang
  • Min-Kyung Yeo
  • Jin-Man Kim
  • Kyung-Cheol Sohn
  • Myung Im
  • Young-Joon Seo
  • Jeung-Hoon Lee
  • Chang-Deok KimEmail author
  • Young LeeEmail author
Original Paper

Abstract

S100A8 and S100A9 are members of the S100 protein family and exist in neutrophils, monocytes, and macrophages. Recent studies have shown that S100A8 and S100A9 are associated with various neoplastic disorders; however, their roles in cutaneous squamous cell carcinoma (SCC) are not well defined. To investigate the expression and function of S100A8 and S100A9 in skin tumors, we examined the expression levels of S100A8 and S100A9 between premalignant and malignant skin tumors and investigated the functional roles of S100A8 and S100A9 in vitro and in vivo using recombinant adenovirus expressing S100A8 or S100A9. The immunopositive staining rates and intensities of S100A8 and S100A9 were higher in SCC than in premalignant skin tumors. When S100A8 and/or S100A9 were overexpressed in SCC12 cells using a recombinant adenovirus, cell growth and motility were increased. Similarly, when mouse skin was intradermally injected with SCC12 cells overexpressing S100A8 and/or S100A9, there were remarkable increases in tumor growth and volume. Both S100A8 and S100A9 are highly expressed in cutaneous SCC and play important roles in tumorigenesis. We suggest that S100A8 and S100A9 may be potential therapeutic targets for the prevention or treatment of SCC in skin.

Keywords

Actinic keratosis Keratoacanthoma S100A8 S100A9 Squamous cell carcinoma 

Notes

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1041389).

Conflict of interest

None to declare.

Supplementary material

403_2014_1453_MOESM1_ESM.pdf (18 kb)
Supplementary material 1 (PDF 18 kb)

References

  1. 1.
    Duan L, Wu R, Ye L et al (2013) S100A8 and S100A9 are associated with colorectal carcinoma progression and contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway. PLoS One 8:e62092PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Fan B, Zhang LH, Jia YN et al (2012) Presence of S100A9-positive inflammatory cells in cancer tissues correlates with an early stage cancer and a better prognosis in patients with gastric cancer. BMC Cancer 12:316PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Foell D, Roth J (2004) Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 50:3762–3771PubMedCrossRefGoogle Scholar
  4. 4.
    Gallagher RP, Hill GB, Bajdik CD et al (1995) Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch Dermatol 131:164–169PubMedCrossRefGoogle Scholar
  5. 5.
    Gebhardt C, Németh J, Angel P, Hess J (2006) S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72:1622–1631PubMedCrossRefGoogle Scholar
  6. 6.
    Guenthner ST, Hurwitz RM, Buckel LJ, Gray HR (1999) Cutaneous squamous cell carcinomas consistently show histologic evidence of in situ changes: a clinicopathologic correlation. J Am Acad Dermatol 41:443–448PubMedCrossRefGoogle Scholar
  7. 7.
    Johnson TM, Rowe DE, Nelson BR, Swanson NA (1992) Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 26:467–484PubMedCrossRefGoogle Scholar
  8. 8.
    Karagas MR, Stannard VA, Mott LA et al (2002) Use of tanning devices and risk of basal cell and squamous cell skin cancers. J Natl Cancer Inst 94:224–226PubMedCrossRefGoogle Scholar
  9. 9.
    Lee Y, Jang S, Min JK et al (2012) S100A8 and S100A9 are messengers in the crosstalk between epidermis and dermis modulating a psoriatic milieu in human skin. Biochem Biophys Res Commun 423:647–653PubMedCrossRefGoogle Scholar
  10. 10.
    Nukui T, Ehama R, Sakaguchi M et al (2008) S100A8/A9, a key mediator for positive feedback growth stimulation of normal human keratinocytes. J Cell Biochem 104:453–464PubMedCrossRefGoogle Scholar
  11. 11.
    Qin F, Song Y, Li Z et al (2010) S100A8/A9 induces apoptosis and inhibits metastasis of CasKi human cervical cancer cells. Pathol Oncol Res 16:353–360PubMedCrossRefGoogle Scholar
  12. 12.
    Rheinwald JG, Beckett MA (1981) Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res 41:1657–1663PubMedGoogle Scholar
  13. 13.
    Schmidt-Hansen B, Ornas D, Grigorian M et al (2004) Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23(32):5487–5495PubMedCrossRefGoogle Scholar
  14. 14.
    Schwartz RA (1994) Keratoacanthoma. J Am Acad Dermatol 30:1–22PubMedCrossRefGoogle Scholar
  15. 15.
    Shi G, Sohn KC, Kim SY et al (2011) Sox9 increases the proliferation and colony-forming activity of outer root sheath cells cultured in vitro. Ann Dermatol 23:138–143PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Turovskaya O, Foell D, Sinha P et al (2008) RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 29:2035–2043PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Vogl T, Leukert N, Barczyk K et al (2006) Biophysical characterization of S100A8 and S100A9 in the absence and presence of bivalent cations. Biochim Biophys Acta 1763:1298–1306PubMedCrossRefGoogle Scholar
  18. 18.
    Voss A, Gescher K, Hensel A et al (2012) Double-stranded RNA induces S100 gene expression by a cycloheximide-sensitive factor. FEBS Lett 586:196–203PubMedCrossRefGoogle Scholar
  19. 19.
    Wang J, Cai Y, Xu H et al (2004) Expression of MRP14 gene is frequently down-regulated in Chinese human esophageal cancer. Cell Res 14:46–53PubMedCrossRefGoogle Scholar
  20. 20.
    Zhu L, Okano S, Takahara M et al (2013) Expression of S100 protein family members in normal skin and sweat gland tumors. J Dermatol Sci 70:211–219PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Dae-Kyoung Choi
    • 1
  • Zheng Jun Li
    • 1
  • In-Kyu Chang
    • 1
  • Min-Kyung Yeo
    • 2
  • Jin-Man Kim
    • 2
  • Kyung-Cheol Sohn
    • 1
  • Myung Im
    • 1
  • Young-Joon Seo
    • 1
  • Jeung-Hoon Lee
    • 1
  • Chang-Deok Kim
    • 1
    Email author
  • Young Lee
    • 1
    Email author
  1. 1.Department of Dermatology and Research Institute for Medical SciencesChungnam National UniversityDaejeonKorea
  2. 2.Department of Pathology, School of MedicineChungnam National UniversityDaejeonKorea

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