TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role

被引:0
作者
Carvalho, Maria Isabel [1 ]
Silva-Carvalho, Ricardo [2 ,3 ]
Prada, Justina [4 ,5 ]
Pinto, Carla [5 ]
Gregorio, Hugo [6 ]
Lobo, Luis [1 ,7 ,8 ]
Pires, Isabel [4 ,5 ]
Queiroga, Felisbina L. [4 ,5 ,8 ]
机构
[1] Lusofona Univ, MVET Res Vet Med, Fac Vet Med, Lisbon Ctr, Lisbon, Portugal
[2] Univ Minho, CEB Ctr Biol Engn, Braga, Portugal
[3] LABBELS Associate Lab, Guimaraes, Portugal
[4] Univ Tras Os Montes & Alto Douro, Vet & Anim Res Ctr CECAV, Vila Real, Portugal
[5] Univ Tras os Montes & Alto Douro, Dept Vet Sci, Vila Real, Portugal
[6] Anicura Ctr Hosp Vet, Porto, Portugal
[7] Onevet Hosp Vet Porto, Porto, Portugal
[8] Univ Porto, Ctr Study Anim Sci, CECA, ICETA, Porto, Portugal
关键词
Angiogenesis; canine mammary tumors; CD31; FoxP3; prognosis; TGF beta; Treg cells; VEGF; GROWTH-FACTOR-BETA; INTRATUMORAL FOXP3 EXPRESSION; BREAST-CANCER; DOWN-REGULATION; T-CELLS; SERUM; METASTASIS; CARCINOMA; BINDING;
D O I
10.1080/01652176.2024.2390941
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Transforming growth factor-beta (TGF beta) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGF beta expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGF beta were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGF beta were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGF beta/FoxP3, TGF beta/VEGF, and TGF beta/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGF beta expression and with concurrent high expression of TGF beta/FoxP3, TGF beta/VEGF, and TGF beta/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGF beta and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.
引用
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页码:1 / 12
页数:12
相关论文
共 61 条
[1]  
Bao Jian, 2009, Zhonghua Zhong Liu Za Zhi, V31, P679
[2]   Gain or loss of TGFβ signaling in mammary carcinoma cells can promote metastasis [J].
Bierie, Brian ;
Moses, Harold L. .
CELL CYCLE, 2009, 8 (20) :3319-3327
[3]   Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer [J].
Biller, B. J. ;
Elmslie, R. E. ;
Burnett, R. C. ;
Avery, A. C. ;
Dow, S. W. .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2007, 116 (1-2) :69-78
[4]   Prognostic significance of transforming growth factor β receptor II in estrogen receptor-negative breast cancer patients [J].
Buck, MB ;
Fritz, P ;
Dippon, J ;
Zugmaier, G ;
Knabbe, C .
CLINICAL CANCER RESEARCH, 2004, 10 (02) :491-498
[5]   Intratumoral FoxP3 expression is associated with angiogenesis and prognosis in malignant canine mammary tumors [J].
Carvalho, Maria Isabel ;
Pires, Isabel ;
Prada, Justina ;
Gregorio, Hugo ;
Lobo, Luis ;
Queiroga, Felisbina L. .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2016, 178 :1-9
[6]   EGFR and microvessel density in canine malignant mammary tumours [J].
Carvalho, Maria Isabel ;
Guimaraes, Maria Joao ;
Pires, Isabel ;
Prada, Justina ;
Silva-Carvalho, Ricardo ;
Lopes, Carlos ;
Queiroga, Felisbina L. .
RESEARCH IN VETERINARY SCIENCE, 2013, 95 (03) :1094-1099
[7]   TGF-β and 'Adaptive' Foxp3+ Regulatory T cells [J].
Chen, WanJun ;
Konkel, Joanne E. .
JOURNAL OF MOLECULAR CELL BIOLOGY, 2010, 2 (01) :30-36
[8]   Crosstalk between TGF-β signaling and miRNAs in breast cancer metastasis [J].
Chen, Wei ;
Zhou, Siying ;
Mao, Ling ;
Zhang, Heda ;
Sun, Dawei ;
Zhang, Junying ;
Li, JIan ;
Tang, Jin-hai .
TUMOR BIOLOGY, 2016, 37 (08) :10011-10019
[9]  
Coban S, 2007, HEPATO-GASTROENTEROL, V54, P1472
[10]   Targeting TGF-β Signaling in Cancer [J].
Colak, Selcuk ;
ten Dijke, Peter .
TRENDS IN CANCER, 2017, 3 (01) :56-71