Nascimento Catarina, Gameiro Andreia, Ferreira João, Correia Jorge, Ferreira Fernando
CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Cancers (Basel). 2021 Jan 1;13(1):117. doi: 10.3390/cancers13010117.
Vascular endothelial growth factor (VEGF-A) plays an essential role in tumor-associated angiogenesis, exerting its biological activity by binding and activating membrane receptors, as vascular endothelial growth factor receptor 1 and 2 (VEGFR-1, VEGFR-2). In this study, serum VEGF-A, VEGFR-1, and VEGFR-2 levels were quantified in 50 cats with mammary carcinoma and 14 healthy controls. The expression of these molecules in tumor-infiltrating lymphocytes (TILs) and in cancer cells was evaluated and compared with its serum levels. Results obtained showed that serum VEGF-A levels were significantly higher in cats with HER2-positive and Triple Negative (TN) Normal-Like subtypes, when compared to control group ( = 0.001, = 0.020). Additionally, serum VEGFR-1 levels were significantly elevated in cats presenting luminal A, HER2-positive and TN Normal-Like tumors ( = 0.011, = 0.048, = 0.006), as serum VEGFR-2 levels ( = 0.010, = 0.046, = 0.005). Moreover, a positive interaction was found between the expression of VEGF-A, VEGFR-1, and VEGFR-2 in TILs and their serum levels ( = 0.002, = 0.003, = 0.003). In summary, these findings point to the usefulness of VEGF-A and its serum receptors assessment in clinical evaluation of cats with HER2-positive and TN Normal-Like tumors, suggesting that targeted therapies against these molecules may be effective for the treatment of these animals, as described in human breast cancer.
血管内皮生长因子(VEGF - A)在肿瘤相关血管生成中起关键作用,它通过与膜受体如血管内皮生长因子受体1和2(VEGFR - 1、VEGFR - 2)结合并激活来发挥其生物学活性。在本研究中,对50只患有乳腺癌的猫和14只健康对照猫的血清VEGF - A、VEGFR - 1和VEGFR - 2水平进行了定量分析。评估了这些分子在肿瘤浸润淋巴细胞(TILs)和癌细胞中的表达,并与其血清水平进行了比较。所得结果显示,与对照组相比,HER2阳性和三阴(TN)正常样亚型的猫血清VEGF - A水平显著更高(P = 0.001,P = 0.020)。此外,呈现管腔A型、HER2阳性和TN正常样肿瘤的猫血清VEGFR - 1水平显著升高(P = 0.011,P = 0.048,P = 0.006),血清VEGFR - 2水平也是如此(P = 0.010,P = 0.046,P = 0.005)。而且,发现TILs中VEGF - A、VEGFR - 1和VEGFR - 2的表达与其血清水平之间存在正相关(P = 0.002,P = 0.003,P = 0.003)。总之,这些发现表明VEGF - A及其血清受体评估在HER2阳性和TN正常样肿瘤猫的临床评估中具有实用性,提示针对这些分子的靶向治疗可能对这些动物的治疗有效,正如在人类乳腺癌中所描述的那样。