Acta Veterinaria Hungarica
Volume/Issue:
Volume 68: Issue 1
Expression levels of angiogenic growth factors in feline squamous cell carcinoma
Authors: Yonca B. Kabak 1 , Mahmut Sozmen 1 , Alparslan K. Devrim 2 , Mert Sudagidan 3 , Funda Yildirim 4 , Tolga Guvenc 1 , Murat Yarim 1 , Yavuz M. Gulbahar 1 , Ishtiaq Ahmed 5 , Efe Karaca 1 , and Sinem Inal 1
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  • 1 Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Kurupelit, 55200 Atakum, Samsun, Turkey
  • 2 Department of Biochemistry, Faculty of Veterinary Medicine, Kırıkkale University, Kırıkkale, Turkey
  • 3 Konya Food and Agriculture University, Kit-Argem, Konya, Turkey
  • 4 Department of Pathology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
  • 5 Department of Pathology, University of Veterinary and Animal Sciences, Lahore, Pakistan
DOI:
https://doi.org/10.1556/004.2020.00005
Page Count:
37–48
Publication Date:
01 Mar 2020
Online Publication Date:
08 May 2020
Article Category:
Research Article
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Abstract

Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the skin in cats. Tumour angiogenesis is the pivotal event for tumour progression and metastasis. We assessed protein and gene expression of angiogenic growth factors including bFGF, VEGF-C, TGF-β, PDGF-A, PDGF-C and PDGFR-α that possibly contribute to the angiogenic phenotype of feline SCC (FSCC) and could, therefore, be a good target in the treatment of SCC. In the present study, a total of 27 FSCC cases were investigated. Tumour cases were histopathologically classified as well differentiated (10/27), moderately differentiated (5/27), and poorly differentiated (12/27). The expression levels of the growth factors were detected using immunohistochemistry and assessed semi-quantitatively. Growth factor expression levels were evaluated at different locations: in the oral region, in areas exposed to solar UV radiation including the ears, eyelids and nasal planum, and other miscellaneous locations. Our findings have revealed that FSCC arising from different anatomical sites of the body and showing differences in aggressiveness, metastasis, and prognosis may be angiogenesis dependent, and angiogenic key regulators could play a role in the development of FSCC.

  • Akhurst, R. J. and Derynck, R. (2001): TGF-β signalling in cancer – a double-edged sword. Trends Cell. Biol. 11 , S44–S51.

  • Al-Dissi, A. N., Haines, D. M., Singh, B. and Kidney, B. A. (2007): Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor associated with tumor cell proliferation in canine cutaneous squamous cell carcinomas and trichoepitheliomas. Vet. Pathol. 44 , 823–830.

    • Search Google Scholar
    • Export Citation

  • Ali, M. A. (2008): Lymphatic microvessel density and the expression of lymphoangiogenic factors in oral squamous cell carcinoma. Med. Princ. Pract. 17 , 486–492.

    • Search Google Scholar
    • Export Citation

  • Alvarez, R. H., Kantarjian, H. M. and Cortes J. E. (2006): Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin. Proc. 81 , 1241–1257.

    • Search Google Scholar
    • Export Citation

  • Andrae, J., Gallini, R. and Betsholtz, C. (2008): Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22 , 1276–1312.

    • Search Google Scholar
    • Export Citation

  • Asahara, T., Bauters, C., Zheng, L. P., Takeshita, S., Bunting, S., Ferrara, N., Symes, J. F. and Isner, J. M. (1995): Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation. 92, 365–371.

    • Search Google Scholar
    • Export Citation

  • Bitzer, M., von Gersdorff, G., Liang, D., Dominguez-Rosales, A., Beg. A. A., Rojkind, M. and Bottinger, E. P. (2000): A mechanism of suppression of TGF-s/SMAD signalling by NF-kappa B/RelA. Gene Dev. 14 , 187–197.

    • Search Google Scholar
    • Export Citation

  • Bran, B., Bran, G., Hörmann, K. and Riedel, F. (2009): The platelet-derived growth factor receptor as a target for vascular endothelial growth factor-mediated anti-angiogenetic therapy in head and neck cancer. Int. J. Oncol. 34 , 255–261.

    • Search Google Scholar
    • Export Citation

  • Breslin, J. W., Pappas, P. J., Cerveira, J. J., Hobson, R. W. and Durán, W. N. (2003): VEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide. Am. J. Physiol. Heart Circ. Physiol. 284, 92–100.

    • Search Google Scholar
    • Export Citation

  • Cao, R., Bjorndahl, M. A., Religa, P., Clasper, S., Garvin, S., Galter, D., Meister, B., Ikomi, F., Tritsaris, K., Dissing, S., Ohhashi, T., Jackson, D. G. and Cao, Y. (2004): PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell. 6, 333–345.

    • Search Google Scholar
    • Export Citation

  • Chen, G., Gharib, T. G., Huang, C. C., Taylor, J. M., Misek, D. E., Kardia, S. L., Giordano, T. J., Iannettoni, M. D., Orringer, M. B., Hanash, S. M. and Beer, D. G. (2002): Discordant protein and mRNA expression in lung adenocarcinomas. Mol. Cell. Proteomics 1 , 304–313.

    • Search Google Scholar
    • Export Citation

  • Cheung, C. Y. and Brace, R. A. (1998): Ovine vascular endothelial growth factor: nucleotide sequence and expression in fetal tissues. Growth Factors 16 , 11–22.

    • Search Google Scholar
    • Export Citation

  • Davies, M., Prime, S. S., Eveson, J. W., Price, N., Ganapathy, A., D'Mello, A. and Paterson, I. C. (2012): Transforming growth factor-β enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes. Int. J. Exp. Pathol. 93 , 148–156.

    • Search Google Scholar
    • Export Citation

  • Dong, J., Grunstein, J., Tejada, M., Peale, F., Frantz, G., Liang, W. C., Bai, W., Yu, L., Kowalski, J., Liang, X., Fuh, G., Gerber, H. P. and Ferrara, N. (2004): VEGF-null cells require PDGFR α signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J. 23, 2800–2810.

    • Search Google Scholar
    • Export Citation

  • Donnem, T., Al-Saad, S., Al-Shibli, K. Delghandi, M. P., Persson, M., Nilsen, M. N., Busund, L. T. and Bremnes, R. M. (2007): Inverse prognostic impact of angiogenic marker expression in tumor cells versus stromal cells in non-small cell lung cancer. Clin. Cancer Res. 13, 6649–6657.

    • Search Google Scholar
    • Export Citation

  • Feng, X. H. and Derynck, R. (2005): Specificity and versatility in TGF-beta signaling through SMADS. Annu. Rev. Cell Dev. Biol. 21 , 659–693.

    • Search Google Scholar
    • Export Citation

  • Ferrara, N. and Davis-Smith, T. (1997): The biology of vascular endothelial growth factor. Endocr. Rev. 18 , 4–25.

  • Galzie, Z., Kinsella, A. R. and Smith, J. A. (1997): Fibroblast growth factors and their receptors. Biochem. Cell Biol. 75 , 669–685.

  • Gazit, A., Igarashi, H., Chiu, I. M., Srinivasan, A., Yaniv, A., Tronick, S. R., Robbins, K. C. and Aaronson, S. A. (1984): Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation. Cell 39 , 89–97.

    • Search Google Scholar
    • Export Citation

  • Gockel, I., Moehler, M., Frerichs, K., Drescher, D., Trinh, T. T., Duenschede, F., Borschitz, T., Schimanski, K., Biesterfeld, S., Herzer, K., Galle, P. R., Lang, H., Junginger, T. and Schimanski, C. C. (2008): Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer. Oncol. Rep. 20 , 845–850.

    • Search Google Scholar
    • Export Citation

  • Goldschmidt, M. H., Dunstan, R. W., Stannard, A. A. von Tscharner, C., Walder, E. J. and Yager, J. A. (1998): Histological Classification of Epithelial and Melanocytic Tumors of the Skin of Domestic Animals, 2nd edition. Armed Forces Institute of Pathology, Washington. pp. 18–21.

    • Search Google Scholar
    • Export Citation

  • Gross, T. L., Ihrke, P. J., Walder, E.J. and Affolter, W. K. (2005): Squamous cell carcinoma. In: Skin Diseases of the Dog and Cat. Clinical and Histopathological Diagnosis. Second edn. Wiley-Blackwell, Iowa. pp. 581–589.

    • Search Google Scholar
    • Export Citation

  • Han, G., Lu, S. L., Li, A. G., He, W., Corless, C. L., Kulesz-Martin, M. and Wang, X. J. (2005): Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J. Clin. Invest. 115, 1714–1723.

    • Search Google Scholar
    • Export Citation

  • Hasina, R., Whipple, M., Martin, L., Kuo, W. P., Ohno-Machado, L. and Lingen, M. W. (2008): Angiogenic heterogeneity in head and neck squamous cell carcinoma: biological and therapeutic implications. Lab. Invest. 88, 342–353.

    • Search Google Scholar
    • Export Citation

  • Heldin, C. H. and Westermark, B. (1999): Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79 , 1283–1316.

    • Search Google Scholar
    • Export Citation

  • Higgins, R. J., Dickinson, P. J., LeCouteur, R. A., Bollen, A. W., Wang, H., Wang, H., Corely, L. J., Moore, L. M., Zang, W. and Fuller, G. N. (2010): Spontaneous canine gliomas: overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping. J. Neuro Oncol. 98 , 49–55.

    • Search Google Scholar
    • Export Citation

  • Hurst, N. J. Jr., Najy, A. J., Ustach, C. V., Movilla, L. and Kim, H. R. (2012): Platelet-derived growth factor-C (PDGF-C) activation by serine proteases; implications for breast cancer progression. Biochem. J. 441 , 909–918.

    • Search Google Scholar
    • Export Citation

  • Ito, M., Yoshida, K., Kyo, E., Ayhan, A., Nakayama, H., Yasui, W., Ito, H. and Tahara, E. (1990): Expression of several growth factors and their receptor genes in human colon carcinomas. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 59, 173–178.

    • Search Google Scholar
    • Export Citation

  • Janot, F., el-Naggar, A. K., Morrison, R. S, Liu, T. J., Taylor, D. L. and Clayman, G. L. (1995): Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation. Int. J. Cancer. 64, 117–123.

    • Search Google Scholar
    • Export Citation

  • Katano, M., Nakamura, M., Fujimoto, K., Miyazaki, K. and Morisaki, T. (1998): Prognostic value of platelet derived growth factor-A (PDGF-A) in gastric carcinoma. Ann. Surg. 227 , 365–371.

    • Search Google Scholar
    • Export Citation

  • Katayama, R., Huelsmeyer, M. K., Marr, A. K., Kurzman, I. D., Thamm, D. H. and Vail, D. M. (2004): Imatinib mesylate inhibits platelet-derived growth factor activity and increases chemosensitivity in feline vaccine-associated sarcoma. Cancer Chemother. Pharmacol. 54, 25–33.

    • Search Google Scholar
    • Export Citation

  • Kitadai, Y., Amioka, T., Haruma, K., Tanaka, S., Yoshihara, M., Sumii, K., Matsutani, N., Yasui, W. and Chayama, K. (2001): Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas. Int. J. Cancer 93 , 662–666.

    • Search Google Scholar
    • Export Citation

  • Kowanetz, M. and Ferrara, N. (2006): Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin. Cancer Res. 12 , 5018–5022.

    • Search Google Scholar
    • Export Citation

  • Lasota, J., Stachura, J. and Miettinen, M. (2006): GISTs with PDGFRA exon 14 mutations represent subset of clinically favourable gastric tumors with epitheloid morphology. Lab. Invest. 86 , 94–100.

    • Search Google Scholar
    • Export Citation

  • Logullo, A. F., Nonogaki, S., Miguel, R. E., Kowalski, L. P., Nishimoto, I. N., Pasini, F. S., Federico, M. H. H., Brentani, R. R. and Brentani, M. M. (2003): Transforming growth factor beta1 (TGFbeta1) expression in head and neck squamous cell carcinoma patients as related to prognosis. J. Oral Pathol. Med. 32 , 139–145.

    • Search Google Scholar
    • Export Citation

  • Man, X. Y., Yang, X. H., Cai, S. Q., Yao, Y. G. and Zheng, M. (2006): Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol. Med. 12 , 127–136.

    • Search Google Scholar
    • Export Citation

  • Millanta, F., Lazzeri, G., Vannozzi, I., Viacava, P. and Poli, A. (2002): Correlation of vascular endothelial growth factor expression to overall survival in feline invasive mammary carcinomas. Vet. Pathol. 39, 690–696.

    • Search Google Scholar
    • Export Citation

  • Miller, M. A., Nelson, S. L., Turk, J. R., Pace, L.W., Brown, T. P., Shaw D. P., Fischer J. R. and Gosser, H. S. (1991): Cutaneous neoplasia in 340 cats. Vet. Pathol. 28, 389–395.

    • Search Google Scholar
    • Export Citation

  • Mincione, G., Di Marcantonio, M. C., Artese, L., Vianale, G., Piccirelli, A., Piccirilli, M., Perrotti, V., Rubini, C., Piattelli, A. and Muraro, R. (2008): Loss of expression of TGF-ß1, TßRI, and TßRII correlates with differentiation in human oral squamous cell carcinomas. Int. J. Oncol. 32 , 323–331.

    • Search Google Scholar
    • Export Citation

  • Montag, M., Dyckhoff, G., Lohr, J., Helmke, B. M., Herrmann, E., Plinkert, P. K. and Herold-Mende, C. (2009): Angiogenic growth factors in tissue homogenates of HNSCC: expression pattern, prognostic relevance and interrelationships. Cancer Sci. 100 , 1210–1218.

    • Search Google Scholar
    • Export Citation

  • Moussai, D., Mitsui, H., Pettersen, J. S., Pierson, K. C., Shah, K. R., Suárez-Fariñas, M., Cardinale, I. R., Bluth, M. J., Krueger, J. G. and Carucci, J. A. (2011): The human cutaneous squamous cell carcinoma microenvironment is characterized by increased lymphatic density and enhanced expression of macrophage-derived VEGF-C. J. Invest. Dermatol. 131, 229–236.

    • Search Google Scholar
    • Export Citation

  • Myoken, Y., Myoken, Y., Okamoto, T., Sato, J. D. and Takada, K. (1994): Immunocytochemical localization of fibroblast growth factor-1 (FGF-1) and FGF-2 in oral squamous cell carcinoma (SCC). J. Oral Pathol. Med. 23, 451–456.

    • Search Google Scholar
    • Export Citation

  • Nakamura, T., Ozawa, S., Kitagawa, Y., Shih, C. H., Ueda, M. and Kitajima, M. (2005): Expression of basic fibroblast growth factor is associated with a good outcome in patients with squamous cell carcinoma of the esophagus. Oncol. Rep. 14 , 617–623.

    • Search Google Scholar
    • Export Citation

  • Nakashio, A., Fujita, N. and Tsuruo, T. (2002): Topotecan inhibits VEGF- and bFGF-induced vascular endothelial cell migration via downregulation of the PI3K-Akt signaling pathway. Int. J. Cancer. 98 , 36–41.

    • Search Google Scholar
    • Export Citation

  • Ninck, S., Reisser, C., Dyckhoff, G., Helmke, B., Bauer, H. and Herold-Mende, C. (2003): Expression profiles of angiogenic growth factors in squamous cell carcinomas of the head and neck. Int. J. Cancer. 106 , 34–44.

    • Search Google Scholar
    • Export Citation

  • Nister, M., Claesson-Welsh, L., Eriksson, A., Heldin, C. H. and Westermark, B. (1991): Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines. J. Biol. Chem. 266 , 16755–16763.

    • Search Google Scholar
    • Export Citation

  • Ostman, A. and Heldin, C. H. (2007): PDGF receptors as targets in tumor treatment. Adv. Cancer Res. 97 , 247–274.

  • Pierce, D. F. Jr., Gorska, A. E., Chytil, A., Meise, K. S., Page, D.L., Coffey, R. J. Jr. and Moses, H. L (1995): Mammary tumor suppression by transforming growth factor-β1 transgene expression. Proc. Natl. Acad. Sci. USA. 92 , 4254–4258.

    • Search Google Scholar
    • Export Citation

  • Ross, R., Raines, E. W. and Bowen-Pope, D. F. (1986): The biology of platelet-derived growth factor. Cell. 46 , 155–169.

  • Sarli, G., Sassi, F., Brunetti, B. Rizzo, A., Diracca, L. and Benazzi, C. (2007): Lymphatic vessels assessment in feline mammary tumors. BMC Cancer. 7 , 7.

    • Search Google Scholar
    • Export Citation

  • Seki, S., Fujiwara, M., Matsuura, M., Fujita, S., Ikeda, H., Asahina, I. and Ikeda, T. (2011): Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors. Oral. Oncol. 47 , 588–593.

    • Search Google Scholar
    • Export Citation

  • Ulloa, L., Doody, J. and Massague, J. (1999): Inhibition of transforming growth factor-s/SMAD signalling by the interferon-γ/STAT pathway. Nature. 397 , 710–713.

    • Search Google Scholar
    • Export Citation

  • Veikkola, T. and Alitalo, K. (1999): VEGFs, receptors and angiogenesis. Semin. Cancer Biol. 9 , 211–220.

  • Wang, X. J. (2001): Role of TGFbeta signaling in skin carcinogenesis. Micros. Res. Tech. 52 , 420–429.

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

  • Wilcock, B. P. (2006): Eye and ear. In: Maxie, M. G. (ed) Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. W. B. Saunders Co., Philadelphia. pp. 534–536.

    • Search Google Scholar
    • Export Citation

  • Witte, D., Thomas, A., Ali, N., Carlson, N. and Younes, M. (2002): Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res. 22 , 1463–1466.

    • Search Google Scholar
    • Export Citation

  • Yoshiji, H., Gomez, D. E., Shibuya, M. and Thorgeirsson, U. P. (1996): Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 56, 2013–2016.

    • Search Google Scholar
    • Export Citation

  • Zhang, J. B., Sun, H. C., Jia, W. D., Zhuang, P. Y., Qian, Y.B., Zhu, X. D., Kong, L. Q., Wang, L., Wu, W. Z. and Tang, Z. Y. (2012): Up-regulation of platelet-derived growth factor-A is responsible for the failure of re-initiated interferon alpha treatment in hepatocellular carcinoma. BMC Cancer. 12 , 439.

    • Search Google Scholar
    • Export Citation

  • Zhang, W., Chu, Y. Q., Ye, Z. Y., Zhao, Z. S. and Tao, H. Q. (2009): Expression of hepatocyte growth factor and basic fibroblast growth factor as prognostic indicators in gastric cancer. Anat. Rec. (Hoboken) 292 , 1114–1121.

    • Search Google Scholar
    • Export Citation
Cover Acta Veterinaria Hungarica
Acta Veterinaria Hungarica
Print ISSN:
0236-6290
Online ISSN:
1588-2705
Keywords:
bFGF; feline; PDGF; squamous cell carcinoma; TGFβ1; VEGF-C

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