Abstract
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 (p = 0.001, p = 0.020). Additionally, serum VEGFR-1 levels were significantly elevated in cats presenting luminal A, HER2-positive and TN Normal-Like tumors (p = 0.011, p = 0.048, p = 0.006), as serum VEGFR-2 levels (p = 0.010, p = 0.046, p = 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 (p = 0.002, p = 0.003, p = 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.
Highlights
Introduction ditions of the Creative CommonsAt-Human breast cancer is the most diagnosed cancer and the leading cause of cancerrelated death in women worldwide [1], being a heterogeneous disease driven by five distinct molecular profiles (Luminal A, Luminal B, HER2-positive, Triple-Negative Normal tribution (CC BY) license.and Basal-Like) [2,3]
(A) Cats with tumors and a positive score for tumor infiltrating lymphocytes (TILs) showed higher serum vascular endothelial growth factor A (VEGF-A), (B) VEGFR-1 and (C) VEGFR-2 levels in comparison with cats that showed a negative score for TILs. (D) Box plot diagrams showing that queens with mammary carcinomas scored as VEGFR-2-positive TILs had high serum VEGF-A and (E) VEGFR-1 levels
The results showed that serum VEGF-A levels were significantly higher in cats with more aggressive mammary carcinoma subtypes, i.e., HER2-positive and Triple Negative (TN) normal-like, in accordance with previous studies in human breast cancer [19,33,34,35]
Summary
Introduction ditions of the Creative CommonsAt-Human breast cancer is the most diagnosed cancer and the leading cause of cancerrelated death in women worldwide [1], being a heterogeneous disease driven by five distinct molecular profiles (Luminal A, Luminal B, HER2-positive, Triple-Negative Normal tribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).and Basal-Like) [2,3]. Human breast cancer is the most diagnosed cancer and the leading cause of cancerrelated death in women worldwide [1], being a heterogeneous disease driven by five distinct molecular profiles (Luminal A, Luminal B, HER2-positive, Triple-Negative Normal tribution (CC BY) license The feline mammary carcinoma (FMC) is a very common neoplasia associated with local recurrence and distant metastasis, resulting in a high mortality rate [4], being HER2-positive and Triple Negative (TN) the most aggressive subtypes [5,6]. VEGF-A is a glycoprotein (45 kDa) that is highly conserved among mammalian species, being expressed by different cell populations, as tumor infiltrating lymphocytes (TILs), macrophages, platelets and cancer cells, promoting capillary network growth and vascular permeability, allowing cancer cells to migrate to distinct organs [15,16,17]. There are four distinct VEGF-A isoforms with 121, 165, 189, and 206 amino acids, as a result of alternative mRNA splicing, with
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