Summary
A natural animal model for human head and neck squamous cell carcinoma (H/N SCC) has not been described. The domestic cat has a high spontaneous occurrence of oropharyngeal SCC, which is similar to the human disease in aggressiveness and incurability. We have developed a cell line (SCCF1) from a laryngeal SSC of a cat. Kerationocytes were maintained in culture for greater than 50 passages. SCCF1 had strong cytokeratin immunohistochemical staining, weak vimentin staining, and no p53 staining. Ultrastructual features included cytokeratin filaments and desmosomes as well as features of anaplasia (irregular cytoplasmic and nuclear margins, surface filopodia, and abnormal intermediate filament production). Karyotype analysis revealed aneuploidy, with a stemline chromosomal number of 34. The cells grew logarithmically for 6 d until confluency. SCCF1 expressed parathyroid hormone-related protein (PTHrP) messenger ribonucleic acid (mRNA) and protein, and secreted the protein into the medium. Treatment of SCCF1 with transforming growth factor-β increased PTHrP production but did not affect PTHrP mRNA stability. Reverse transcriptase-polymerase chain reaction was used to amplify a 282-base pair region of feline PTHrP mRNA, encoding portions of the pre-pro and coding regions. The complementary deoxyribonucleic acid (cDNA) was cloned and sequenced. The cDNA and the predicted amino acid sequences had a high degree of homology to human and canine PTHrP RT-PCR was used to confirm alternate spicing of PTHrP mRNA for translation of PTHrP 1–139 and PTHrP 1–141. The SCCF1 cell line will permit mechanistic experiments on genetic dysregulation in neoplastic keratinocytes of the feline oropharynx, and development of an in vitro model for H/N cancer.
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References
Bochsler, J.; Winsor, C.; Houle, C.; Shearn, V. A concise survey of neoplasia in domestic cats by tumor type and body location. Vet. Pathol. 37:534; 2000.
Boyle, J. O.; Hakim, J.; Koch, W., et al. The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res. 53:4477–4480; 1993.
Caulin, C.; Scholl, F. G.; Frontelo, P.; Gamallo, C.; Quintanilla, M. Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-beta 1 induces an epithelial—mesenchymal trans-differentiation and a spindle tumoral phenotype. Cell Growth Differ. 6:1027–1035; 1995.
Cheville, N. F. Neoplasia Ultrastructural pathology: an introduction to interpretation. Ames: Iowa State University Press; 1994;229–273.
Cotter, S. M. Oral pharygeal neoplasms in the cat. J. Am. Anim. Hosp. Assoc. 17:917–920; 1981.
Eguchi, G.; Kodama, R. Transdifferentiation. Curr. Opin. Cell Biol. 5:1023–1028; 1993.
Foley, J.; Wysolmerski, J. J.; Broadus, A. E.; Philbrick, W. M. Parathyroid hormone-related protein gene expression in human squamous carcinoma cells is repressed by mutant isoforms of p53. Cancer Res. 56:4056–4062; 1996.
Grill, V.; Martin, T. J. Parathyroid hormone-related protein as a cause of hypercalcemia of malignancy. In: Bilezikian, J. P.; Marcus, R.; Levine, M. A., ed. The parathyroids. New York: Raven Press; 1994:295–311
Hawkins, B. L.; Heniford, B. W.; Ackermann, D. M.; Leonberger, M.; Martinez, S. A.; Hendler, F. J. 4NQO carcinogenesis: a mouse model of oral cavity squamous cell carcinoma. Head Neck 16:424–432; 1994.
Henderson, D. W.; Papadimitrou, J. M.; Coleman, M. Squamous and transitional cell tumours. Ultrastructural appearance of tumors: diagosis and classification of human neoplasia by electron microscopy. Edinburgh Churchill Livingstone; 1986:75–87
Manenti, G.; Peissel, B.; Gariboldi, M., et al. A cancer modifier role for parathyroid hormone-related protein. Oncogene 19:5324–5328; 2000.
Marefat, M. P. The effect of the short dose schedule of DMBA application in inducing lingual neoplasia in inbred Syrian hamsters. J. Oral Pathol. 14:383–389; 1985.
Martin, T. J.; Allan, E. H.; Caple, I. W., et al. Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action. Recent Prog. Horm. Res. 45:467–502; 1989.
Merryman, J. I.; Capen, C. C.; McCauley, L. K.; Werkmeister, J. R.; Suter, M. M.; Rosol, T. J. Regulation of parathyroid hormone-related protein production by a squamous carcinoma cell line in vitro. Lab. Invest. 69:347–354; 1993.
Merryman, J. I.; DeWille, J. W.; Werkmeister, J. R.; Capen, C. C.; Rosol, T. J. Effects of transforming growth factor-beta on parathyroid hormone-related protein production and ribonucleic acid expression by a squamous carcinoma cell line in vitro. Endocrinology 134:2424–2430; 1994.
Murphy, W. J.; Sun, S.; Chen, Z.; Yuhki, N.; Hirschmann, D.; Menotti-Raymond, M.; O'Brien, S. J. A radiation hybrid map of the cat genome: implications for comparative mapping. Genome Res. 10:691–702; 2000.
Nauta, J. M.; Roodenburg, J. L.; Nikkels, P. G.; Witjes, M. J.; Vermey, A. Epithelial dysplasia and squamous cell carcinoma of the Wistar rat palatal mucosa: 4NOO model. Head Neck 18:441–449; 1996.
O'Brien, S. J.; Nash, W. G. Genetic mapping in mammals: chromosome map of domestic cat. Science 216:257–265; 1982.
Philbrick, W. M.; Wysolmerski, J. J.; Galbraith, S., et al. Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol. Rev. 76:127–173; 1996.
Piek, E.; Moustakas, A.; Kurisaki, A.; Heldin, C. H.; ten Dijke, P. TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J. Cell Sci. 112(Part 24):4557–4568; 1999.
Ralston, S. H.; Gallacher, S. J.; Patel, U.; Campbell, J.; Boyle, I. T. Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patients. Ann. Intern. Med. 112:449–504; 1990.
Raybaud-Diogene, H.; Tetu, B.; Morency, R.; Fortin, A.; Monteil, R. A. p53 overexpression in head and neck squamous cell carcinoma: review of the literature. Eur. J. Cancer B Oral Oncol. 32B:143–149; 1996.
Rikimaru, K.; Matsumoto, F.; Hayashi, E.; Bando, H.; Nagayama, M. Evaluation of serum concentration of parathyroid hormone-related protein and its implication in hypercalcemia in squamous cell carcinoma of the head and neck. Int. J. Oral Maxillofac. Surg. 24:365–368; 1995.
Rosol, T. J.; Steinmeyer, C. L.; McCauley, L. K.; Grone, A.; DeWille, J. W.; Capen, C. C. Sequences of the cDNAs encoding canine parathyroid hormone-related protein and parathyroid hormone. Gene 160:241–243; 1995.
Scioscia, K. A.; Snyderman, C. H.; D'Amico, F.; Comsa, S.; Rueger, R.; Light, B. Effects of arachidonic acid metabolites in a murine model of squamous cell carcinoma. Head Neck 22:149–155; 2000.
Slaga, T. J.; Gimenez-Conti, I. B. An animal model for oral cancer. J. Natl. Cancer Inst. Monogr. 55–62; 1992.
Somers K. D.; Merrick, M. A.; Lopez, M. E.; Incognito, L. S.; Schechter, G. L.; Casey, G. Frequent p53 mutations in head and neck cancer. Cancer Res. 52:5997–6000; 1992.
The American Cancer Society. Oral cavity and oropharyngeal cancer. http://www.cancer.org. 2001.
Thiery, J. P.; Chopin, D. Epithelial cell plasticity in development and tumor progression. Cancer Metastasis Rev. 18:31–42; 1999.
Weckmann, M. T.; Grone, A.; Capen, C. C.; Rosol, T. J. Regulation of parathyroid hormone-related protein secretion and mRNA expression in normal human keratinocytes and a squamous carcinoma cell line. Exp. Cell Res. 232:79–89; 1997.
Werkmeister, J. R.; Blomme, E. A.; Weckmann, M. T., et al. Effect of transforming growth factor-betal on parathyroid hormone-related protein secretion and mRNA expression by normal human keratinocytes in vitro. Endocrine 8:291–299; 1998.
Werkmeister, J. R.; Merryman, J. I.; McCauley, L. K.; Horton, J. E.; Capen, C. C.; Rosol, T. J. Parathyroid hormone-related protein production by normal human keratinocytes in vitro. Exp. Cell Res. 208:68–74; 1993.
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Tannehill-Gregg, S., Kergosien, E. & Rosol, T.J. Feline head and neck squamous cell carcinoma cell line: Characterization, production of parathyroid hormone-related protein, and regulation by transforming growth factor-β. In Vitro Cell.Dev.Biol.-Animal 37, 676–683 (2001). https://doi.org/10.1290/1071-2690(2001)037<0676:FHANSC>2.0.CO;2
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DOI: https://doi.org/10.1290/1071-2690(2001)037<0676:FHANSC>2.0.CO;2