Browse > Article
http://dx.doi.org/10.4142/jvs.2021.22.e62

Metastasis prognostic factors and cancer stem cell-related transcription factors associated with metastasis induction in canine metastatic mammary gland tumors  

Kim, Saetbyul (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Bok, Eunyeong (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Lee, Sangyeob (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Lee, Hyeon-Jeong (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Choe, Yongho (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Kim, Na-Hyun (Gyeongnam Department of Environment & Toxicology, Korea Institute of Toxicology)
Lee, Won-Jae (Department of Veterinary Obstetrics, College of Veterinary Medicine, Kyungpook National University)
Rho, Gyu-Jin (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Lee, Sung-Lim (Department of Veterinary Obstetrics, College of Veterinary Medicine, Gyeongsang National University)
Publication Information
Journal of Veterinary Science / v.22, no.5, 2021 , pp. 62.1-62.13 More about this Journal
Abstract
Background: Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies. Objectives: We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs. Methods: Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis. Results: The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant. Conclusions: Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1, can be used as reliable metastasis factors for canine MGT and therapeutic strategy.
Keywords
Canine; mammary gland tumor; metastasis; prognostic molecular markers; stem cell markers;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bareiss PM, Paczulla A, Wang H, Schairer R, Wiehr S, Kohlhofer U, et al. SOX2 expression associates with stem cell state in human ovarian carcinoma. Cancer Res. 2013;73(17):5544-5555.   DOI
2 Pham DL, Scheble V, Bareiss P, Fischer A, Beschorner C, Adam A, et al. SOX2 expression and prognostic significance in ovarian carcinoma. Int J Gynecol Pathol. 2013;32(4):358-367.   DOI
3 Restucci B, Papparella S, De Vico G, Maiolino P. E cadherin expression in normal and neoplastic canine mammary gland. J Comp Pathol. 1997;116(2):191-202.   DOI
4 Ren X, Long M, Li Z, Wu B, Jin T, Tu C, et al. Oncogene PRR14 promotes breast cancer through activation of PI3K signal pathway and inhibition of CHEK2 pathway. Cell Death Dis. 2020;11(6):464.   DOI
5 Reis AL, Carvalheira J, Schmitt FC, Gartner F. Immunohistochemical study of the expression of E-cadherin in canine mammary tumours. Vet Rec. 2003;152(20):621-624.   DOI
6 Rosette C, Roth RB, Oeth P, Braun A, Kammerer S, Ekblom J, et al. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis. 2005;26(5):943-950.   DOI
7 Di D, Chen L, Wang L, Sun P, Liu Y, Xu Z, et al. Downregulation of human intercellular adhesion molecule-1 attenuates the metastatic ability in human breast cancer cell lines. Oncol Rep. 2016;35(3):1541-1548.   DOI
8 Li F, Zhang C, Fu L. PRR14 overexpression promotes cell growth, epithelial to mesenchymal transition and metastasis of colon cancer via the AKT pathway. PLoS One. 2019;14(10):e0218839.   DOI
9 Lu X, Gao C, Liu C, Zhuang J, Su P, Li H, et al. Identification of the key pathways and genes involved in HER2-positive breast cancer with brain metastasis. Pathol Res Pract. 2019;215(8):152475.   DOI
10 J Sedano M, I Ramos E, Choudhari R, L Harrison A, Subramani R, Lakshmanaswamy R, et al. Hypoxanthine phosphoribosyl transferase 1 is upregulated, predicts clinical outcome and controls gene expression in breast cancer. Cancers (Basel). 2020;12(6):1522.   DOI
11 Han N, Li W, Zhang M. The function of the RNA-binding protein hnRNP in cancer metastasis. J Cancer Res Ther. 2013;9 Suppl:S129-S134.
12 Webster JD, Yuzbasiyan-Gurkan V, Trosko JE, Chang CC, Kiupel M. Expression of the embryonic transcription factor Oct4 in canine neoplasms: a potential marker for stem cell subpopulations in neoplasia. Vet Pathol. 2007;44(6):893-900.   DOI
13 Zhao W, Ji X, Zhang F, Li L, Ma L. Embryonic stem cell markers. Molecules. 2012;17(6):6196-6236.   DOI
14 Varallo GR, Gelaleti GB, Maschio-Signorini LB, Moschetta MG, Lopes JR, De Nardi AB, et al. Prognostic phenotypic classification for canine mammary tumors. Oncol Lett. 2019;18(6):6545-6553.
15 Chaiyawat P, Phanphaisarn A, Sirikaew N, Klangjorhor J, Thepbundit V, Teeyakasem P, et al. IMPDH2 and HPRT expression and a prognostic significance in preoperative and postoperative patients with osteosarcoma. Sci Rep. 2021;11(1):10887.   DOI
16 Li X, Wang J, Xu Z, Ahmad A, Li E, Wang Y, et al. Expression of Sox2 and Oct4 and their clinical significance in human non-small-cell lung cancer. Int J Mol Sci. 2012;13(6):7663-7675.   DOI
17 Gatti M, Solari A, Pattarozzi A, Campanella C, Thellung S, Maniscalco L, et al. In vitro and in vivo characterization of stem-like cells from canine osteosarcoma and assessment of drug sensitivity. Exp Cell Res. 2018;363(1):48-64.   DOI
18 Wilson H, Huelsmeyer M, Chun R, Young KM, Friedrichs K, Argyle DJ. Isolation and characterisation of cancer stem cells from canine osteosarcoma. Vet J. 2008;175(1):69-75.   DOI
19 Yang F, Zhang J, Yang H. OCT4, SOX2, and NANOG positive expression correlates with poor differentiation, advanced disease stages, and worse overall survival in HER2+ breast cancer patients. Onco Targets Ther. 2018;11(11):7873-7881.   DOI
20 Gwak JM, Kim M, Kim HJ, Jang MH, Park SY. Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as an indicator for poor clinical outcome and tamoxifen resistance. Oncotarget. 2017;8(22):36305-36318.   DOI
21 Moschetta MG, Maschio LB, Jardim-Perassi BV, Gelaleti GB, Lopes JR, Leonel C, et al. Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors. Oncol Rep. 2015;33(5):2345-2353.   DOI
22 Tavasoly A, Golshahi H, Rezaie A, Farhadi M. Classification and grading of canine malignant mammary tumors. Vet Res Forum 2013;4(1):25-30.
23 Cassali GD, Lavalle GE, de Nardi AB, Ferreira E, Bertagnolli AC, Estrela-Lima A, et al. Consensus for the diagnosis, prognosis and treatment of canine mammary tumors. Braz J Vet Pathol. 2011;4(2):153-180.
24 Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704-715.   DOI
25 Wang Q, He W, Lu C, Wang Z, Wang J, Giercksky KE, et al. Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res 2009;29(4):1233-1241.
26 Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, et al. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res. 2012;174(1):130-135.   DOI
27 Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ, Guan XY. Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer. 2002;95(11):2346-2352.   DOI
28 Sarli G, Preziosi R, De Tolla L, Brunetti B, Benazzi C. E-cadherin immunoreactivity in canine mammary tumors. J Vet Diagn Invest. 2004;16(6):542-547.   DOI
29 Rodo A, Malicka E. E-cadherin immunohistochemical expression in mammary gland neoplasms in bitches. Pol J Vet Sci. 2008;11(1):47-54.
30 El-Sherbiny YM, Cox MC, Ismail ZA, Shamsuddin AM, Vucenik I; EI-Sherbiny YM. G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6). Anticancer Res 2001;21(4A):2393-2403.
31 Wei F, Ding L, Wei Z, Zhang Y, Li Y, Qinghua L, et al. Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget. 2016;7(51):85259-85272.   DOI
32 Vargas TH, Pulz LH, Barra CN, Kleeb SR, Xavier JG, Catao-Dias JL, et al. Immunohistochemical expression of the pluripotency factor OCT4 in canine mast cell tumours. J Comp Pathol. 2015;153(4):251-255.   DOI
33 Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010;70(24):10433-10444.   DOI
34 Hatefi N, Nouraee N, Parvin M, Ziaee SA, Mowla SJ. Evaluating the expression of oct4 as a prognostic tumor marker in bladder cancer. Iran J Basic Med Sci 2012;15(6):1154-1161.
35 Chen Y, Huang Y, Huang Y, Chen J, Wang S, Zhou J. The prognostic value of SOX2 expression in non-small cell lung cancer: a meta-analysis. PLoS One. 2013;8(8):e71140.   DOI
36 Aponte PM, Caicedo A. Stemness in cancer: stem cells, cancer stem cells, and their microenvironment. Stem Cells Int. 2017;2017:5619472.   DOI
37 Hart AH, Hartley L, Parker K, Ibrahim M, Looijenga LH, Pauchnik M, et al. The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer. 2005;104(10):2092-2098.   DOI
38 Yu B, Cai H, Xu Z, Xu T, Zou Q, Gu M. Expressions of stem cell transcription factors Nanog and Oct4 in renal cell carcinoma tissues and clinical significance. Artif Cells Nanomed Biotechnol. 2016;44(8):1818-1823.   DOI
39 Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012;29(2):878-885.   DOI
40 Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3(12):895-902.   DOI
41 Monk M, Holding C. Human embryonic genes re-expressed in cancer cells. Oncogene. 2001;20(56):8085-8091.   DOI
42 Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun. 2009;383(2):157-162.   DOI
43 Misdorp W, Else R W, Hellmen E, Lipscomb TP. Histological Classification of Mammary Tumors of the Dog and the Cat. Washington, D.C.: Armed Forces Institute of Pathology and the American Registry of Pathology and the World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology; 1999, 11-29.
44 Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol 1993;4(4):219-229. PUBMED