Musa Özgür ÖZYİĞİT, Deniz NAK, Hasan AKŞİT, Sevda İnan ÖZTÜRKOĞLU, Gözde ŞİMŞEK, Ender UZABACI, Yavuz NAK, Kamil SEYREK

The effects of vincristine sulfate on expression of galectin-3, Bcl-2, and carbohydrate structures specific for EEL, GSL-1, and RCA-1 lectins in bitches with naturally occurring canine transmissible venereal tumor

Vincristine sulfate is one of the most effective chemical agents used in canine transmissible venereal tumor (CTVT) chemotherapy. Its therapeutic effectiveness is pronounced and significant at the beginning of treatment. The present study was designed to investigate vincristine sulfate treatment and the relationship between CTVT tumor regression and apoptosis [estimated by TdT-mediated dUTP-biotin nick end labeling (TUNEL)], galectin-3 (H-160), Bcl-2 (N-9), and lectin [EEL (B-135), GSL I (L-1100), and RCA I (BA-0084)] expression using immunohistochemical staining in 20 bitches with naturally occurring CTVTs. Evaluation was semiquantitatively performed by HSCORE values using light microscopy. All observed staining was intracytoplasmic and increased endothelial staining was noted with the Bcl-2 marker in tumor vessels. Apoptosis, TUNEL, and lectin scoring was higher in vincristine sulfate-treated tumors than in untreated tumors, while expression of antiapoptotic factors galectin-3 and Bcl-2 were lower in treated than in untreated CTVTs. These results show that galectin-3, Bcl-2, and lectins (EEL, GSL-1, and RCA-1) are suitable indicators/markers for CTVT tumor regression after treatment with vincristine sulfate.

Keywords:

Key words: Transmissible venereal tumor, Bcl-2, galectin-3, vincristine sulfate, TUNEL, immunohistochemistry, lectins,

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Stockmann D, Ferrari HF, Andrade AL, Cardoso TC, Luvizotto MCR. Detection of the tumour suppressor gene TP53 and expression of p53, Bcl-2 and p63 proteins in canine transmissible venereal tumour. Vet Comp Oncol 2011; 9: 251–259.
Nak D, Nak Y, Cangul IT, Tuna B. A clinico-pathological study on the effect of vincristine on transmissible venereal tumour in dogs. J Vet Med A Physiol Pathol Clin Med 2005; 52: 366–370.
Rui K, Eimi S, Okamura T, Watanabe S, Hasegawa A. Expression of Bcl-2 in feline lymphoma cell lines. Vet Clin Pathol 2008; 37: 57–
Coli A, Bigotti G, Zucchetti F, Negro F, Massi G. Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia. Histopathology 2002; 40: 80–87.
Ishibashi H, Suzuki T, Suzuki S, Moriya T, Kaneko C, Takizawa T, Sunamori M, Handa M, Kondo T, Sasano H. Sex steroid hormone receptors in human thymoma, J Clin Endocrinol Metab 2003; 88: 2309–2317.
Özalp GR, Zik B, Bastan A, Peker S, Özdemir-Salci ES, Bastan I, Darbaz I, Salar S, Karakas K. Vincristine modulates the expression of Ki67 and apoptosis in naturally occurring canine transmissible venereal tumor (TVT). Biotech Histochem 2012; 87: 325–330.
Boscos CM, Ververidis HN. Canine TVT: clinical findings, diagnosis and treatment. In: Proceedings of the WSAVAFECAVA-HVMS World Congress. Rhodes, Greece: WSAVAFECAVA-HVMS; 2004. pp. 758–761.
Cohen D. The canine transmissible venereal tumor: a unique result of tumor progression. Adv Cancer Res 1985; 43: 75–112.
Pir Yağci İ, Kalender H. Bir erkek köpekte transmissible venereal tümör (TVT) olgusunun vincristine sulphate ile sağaltımı. Kafkas Üniv Vet Fak Derg 2008; 14: 105–108 (in Turkish).
Varughese EE, Singla VK, Ratnakaran U, Gandotra VK. Successful management of metastatic transmissible venereal tumour to skin of mammary region. Reprod Domest Anim 2012; 47: 366–369.
Jeon BS, Yoon BI. Altered expression of cellular Bcl-2 in the progression of hamster cholangiocarcinogenesis. ScientificWorldJournal 2012; 2012: 385840.
Goping IS, Gross A, Lavoie JN, Nguyen M, Jemmerson R, Roth K, Korsmeyer SJ, Shore GC. Regulated targeting of Bax to mitochondria. J Cell Biol 1998; 143: 207–215.
Kirkin V, Joos S, Zörnig M. The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta 2004; 1: 229–249.
Eissa S, Labib R, Khalifa A, Swelam N, Khalil F, El-Shenawy AM. Regulators of apoptosis in human breast cancer. Clin Biochem 1999; 32: 321–326.
Choi YK, Hong SH, Kim BH, Kim HC, Woo HJ, Kim DY. Immunohistochemical expression of galectin-3 in canine mammary tumours. J Comp Pathol 2004; 131: 242–245.
De Oliveira JT, de Matos AJF, Gomes J, Vilanova M, Hespanhol V, Manninen A, Rutteman G, Chammas R, Gärtner F, Bernardes ES. Coordinated expression of galectin-3 and galectin-3binding sites in malignant mammary tumors: implications for tumor metastasis. Glycobiology 2010; 20: 1341–1352.
Yoshii T, Fukumori T, Honjo Y, Inohara H, Kim HR, Raz A. Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. J Biol Chem 2002; 77: 6852–6857.
Iurisci I, Tinari N, Natoli C, Angelucci D, Cianchetti E, Iacobelli S. Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res 2000; 6: 1389–1393.
Pacis RA, Pilat MJ, Pienta KJ, Wojno K, Raz A, Hogan V, Cooper CR. Decreased galectin-3 expression in prostate cancer. Prostate 2000; 44: 118–123.
Bresalier RS, Mazurek N, Sternberg LR, Byrd JC, Yunker CK, Nangia-Makker P, Raz A. Metastasis of human colon cancer is altered by modifying expression of the beta-galactosidebinding protein galectin 3. Gastroenterology 1998; 115: 287– 2
Lotz MM, Andrews CW, Korzelius CA, Lee EC, Steele GD, Clarke A, Mercurio AM. Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci U S A 1993; 90: 3466– 34
Fernández PL, Merino MJ, Gómez M, Campo E, Medina T, Castronovo V, Sanjuán X, Cardesa A, Liu FT, Sobel ME. Galectin-3 and laminin expression in neoplastic and nonneoplastic thyroid tissue. J Pathol 1997; 181: 80–86.
Castronovo V, Van Den Brûle FA, Jackers P, Clausse N, Liu FT, Gillet C, Sobel ME. Decreased expression of galectin-3 is associated with progression of human breast cancer. J Pathol 1996; 179: 43–48.
Woo HJ, Joo HG, Song SW, Sohn YS, Chae C. Immunohistochemical detection of galectin-3 in canine gastric carcinomas. J Comp Path 2001; 124: 216–218.
Nangia-Makker P, Honjo Y, Sarvis R, Akahani S, Hogan V, Pienta KJ, Raz A. Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol 2000; 156: 899– 90
Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563–572.
Niikawa S, Hara A, Shirakami S, Zhang W, Sakai N, Yamada H, Shimokawa K. Relationship between Ricinus communis agglutinin-1 binding and nucleolar organizer regions in human glioamas. Neurol Med Chir 1993; 33: 345–349.
Toyoda M, Yamazaki-Inoue M, Itakura Y, Kuno A, Ogawa T, Yamada M, Akutsu H, Takahashi Y, Kanzaki S, Narimatsu H et al. Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells 2011; 16: 1–11.
Wu AM, Wu JH, Chen YY, Song SC, Kabat EA. Further characterization of the combining sites of Bandeiraea (Griffonia) simplicifolia lectin-I, isolectin A (4). Glycobiology 1999; 9: 1161–1170.