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Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line

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Abstract

Osteopontin (OPN) is a secreted glycoprotein implicated to function in cancer development and metastasis. Although elevated expression of OPN are observed in cancer cells of various types, in some cases, only the cells in the stromal region surrounding the tumor express OPN, suggesting distinct functional roles for this protein derived from host cells and from cancer cells. To provide a model for addressing the functions and mechanisms of host-derived OPN in cancer progression and metastasis, a cutaneous squamous cell carcinoma cell line (ONSC) that lacks the OPN gene, Spp1, was established. This line of cells was derived from a squamous cell carcinoma that developed in a female, OPN-null mouse subjected to two-stage skin carcinogenesis. Morphologically, ONSC cells resemble epithelial cells, and they express the epithelial markers, K1, K14, and p63, as confirmed by immunohistochemical analyses. Genomic analyses indicate the presence of mutated H-Ras and p53 genes. ONSC cells form colonies in soft agar and, subcutaneously injected into athymic nude mice, develop into squamous cell carcinomas that metastasize to the lungs. Lacking OPN expression, these squamous cell carcinoma cells provide a model to address the function of host OPN in the context of cancer progression and metastasis.

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References

  • Brown L. F.; Papadopoulos-Sergiou A.; Berse B.; Manseau E. J.; Tognazzi K.; Perruzzi C. A.; Dvorak H. F.; Senger D. R. Osteopontin expression and distribution in human carcinomas. Am. J. Pathol. 145: 610–623; 1994.

    CAS  PubMed  Google Scholar 

  • Chang P. L.; Prince C. W. 1alpha, 25-dihydroxyvitamin D3 stimulates synthesis and secretion of nonphosphorylated osteopontin (secreted phosphoprotein 1) in mouse JB6 epidermal cells. Cancer Res. 51: 2144–2150; 1991.

    CAS  PubMed  Google Scholar 

  • Chang P. L.; Tucker M. A.; Hicks P. H.; Prince C. W. Novel protein kinase C isoforms and mitogen-activated kinase kinase mediate phorbol ester-induced osteopontin expression. Intl. J. Biochem. Cell Biol. 34: 1142–1151; 2002.

    Article  CAS  Google Scholar 

  • Colburn N. H. Tumor promoter produces anchorage independence in mouse epidermal cells by an induction mechanism. Carcinogenesis 1: 951–954; 1980.

    Article  CAS  PubMed  Google Scholar 

  • Crawford H. C.; Matrisian L. M.; Liaw L. Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo. Cancer Res. 58: 5206–5215; 1998.

    CAS  PubMed  Google Scholar 

  • Frame S.; Crombie R.; Liddell J.; Stuart D.; Linardopoulos S.; Nagase H.; Portella G.; Brown K.; Street A.; Akhurst R.; Balmain A. Epithelial carcinogenesis in the mouse: correlating the genetics and the biology. Philos. Trans. R. Soc. Lond. B, Biol. Sci. 353: 839–845; 1998.

    Article  CAS  Google Scholar 

  • Hoshi N.; Sugino T.; Suzuki T. Regular expression of osteopontin in granular cell tumor: distinctive feature among Schwannian cell tumors. Pathol. Int. 55: 484–490; 2005.

    Article  CAS  PubMed  Google Scholar 

  • Hsieh Y. H.; Juliana M. M.; Hicks P. H.; Feng G.; Elmets C.; Liaw L.; Chang P. L. Papilloma development is delayed in osteopontin-null mice: implicating an antiapoptosis role for osteopontin. Cancer Res. 66: 7119–7127; 2006.

    Article  CAS  PubMed  Google Scholar 

  • Liaw L.; Birk D. E.; Ballas C. B.; Whitsitt J. S.; Davidson J. M.; Hogan B. L. Altered wound healing in mice lacking a functional osteopontin gene (spp 1). J. Clin. Invest. 101: 1468–1478; 1998.

    CAS  PubMed  Google Scholar 

  • McGarrity G. J.; Steiner T.; Vanaman V. Detection of mycoplasma infection of cell cultures by DNA fluorochrome staining. In: Tully J. G.; Razin E. (eds) Methods in mycoplasmology. Academic, New York, pp 155–208; 1983.

    Google Scholar 

  • Melnikova V. O.; Pacifico A.; Chimenti S.; Peris K.; Ananthaswamy H. N. Fate of UVB-induced p53 mutations in SKH-hr1 mouse skin after discontinuation of irradiation: relationship to skin cancer development. Oncogene 24: 7055–7063; 2005.

    Article  CAS  PubMed  Google Scholar 

  • Menzin J.; Lines L. M.; Manning L. N. The economics of squamous cell carcinoma of the head and neck. Curr. Opin. Otolaryngol. Head Neck Surg. 15: 68–73; 2007.

    Article  PubMed  Google Scholar 

  • Nelson M. A.; Futscher B. W.; Kinsella T.; Wymer J.; Bowden G. T. Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors. Proc. Natl. Acad. Sci. USA 89: 6398–6402; 1992.

    Article  CAS  PubMed  Google Scholar 

  • Reis-Filho J. S.; Torio B.; Albergaria A.; Schmitt F. C. p63 expression in normal skin and usual cutaneous carcinomas. J. Cutan. Pathol. 29: 517–523; 2002.

    Article  PubMed  Google Scholar 

  • Rittling S. R.; Chambers A. F. Role of osteopontin in tumour progression. Br. J. Cancer 90: 1877–1881; 2004.

    Article  CAS  PubMed  Google Scholar 

  • Ruggeri B. A.; Bauer B.; Zhang S. Y.; Klein-Szanto A. J. Murine squamous cell carcinoma cell lines produced by a complete carcinogenesis protocol with benzo[a]pyrene exhibit characteristic p53 mutations and the absence of H-ras and cyl 1/cyclin D1 abnormalities. Carcinogenesis 15: 1613–1619; 1994.

    Article  CAS  PubMed  Google Scholar 

  • Shin S. I.; Freedman V. H.; Risser R.; Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc. Natl. Acad. Sci. USA 72: 4435–4439; 1975.

    Article  CAS  PubMed  Google Scholar 

  • Sun Y.; Nakamura K.; Hegamyer G.; Dong Z.; Colburn N. No point mutation of Ha-ras or p53 genes expressed in preneoplastic-to-neoplastic progression as modeled in mouse JB6 cell variants. Mol. Carcinog. 8: 49–57; 1993.

    Article  PubMed  Google Scholar 

  • Tunio G. M.; Hirota S.; Nomura S.; Kitamura Y. Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer. Arch. Pathol. Lab. Med. 122: 1087–1090; 1998.

    CAS  PubMed  Google Scholar 

  • Wai P. Y.; Kuo P. C. Osteopontin: regulation in tumor metastasis. Cancer Metastasis Rev. 27: 103–118; 2008.

    Article  CAS  PubMed  Google Scholar 

  • Weinberg A. S.; Ogle C. A.; Shim E. K. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol. Surg. 33: 885–899; 2007.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Patricia Hicks for her technical assistance and Dr. Michael Ruppert for shared reagents. We greatly appreciate Dr. Don Hill for reviewing the manuscript. This work was partially supported by U.S. National Cancer Institute grant R01 CA90920 (P.-L. C.), and the Pi-Ling Chang Research Support.

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Authors and Affiliations

  1. Department of Nutrition Sciences, University of Alabama at Birmingham, 1530 3rd Avenue South, 311 Webb, Birmingham, AL, 35294, USA

    Yu-Hua Hsieh & Pi-Ling Chang

  2. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    M. Margaret Juliana

  3. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Pi-Ling Chang

Authors
  1. Yu-Hua Hsieh
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  2. M. Margaret Juliana
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  3. Pi-Ling Chang
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Correspondence to Pi-Ling Chang.

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Editor: J. Denry Sato

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Hsieh, YH., Juliana, M.M. & Chang, PL. Establishment and characterization of an osteopontin-null cutaneous squamous cell carcinoma cell line. In Vitro Cell.Dev.Biol.-Animal 46, 87–91 (2010). https://doi.org/10.1007/s11626-009-9248-8

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  • DOI: https://doi.org/10.1007/s11626-009-9248-8

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