Deregulation of VEGFR-2 and PDGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis

Abstract

Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived growth factor receptor (PDGFR), and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (n = 11), tumors with lymph node metastasis (LNM) (n = 10), and tumors with lung metastasis (LM) (n = 5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression.

Investigation of the Prognostic Significance of Vasculogenic Mimicry and Its Inhibition by Sorafenib in Canine Mammary Gland Tumors

“…Patients with at least stage III and tumor histological grade II disease received adjuvant treatment, and patients with metastatic disease at diagnosis were treated with chemotherapy. Clinical follow-up was performed according to Dos Anjos et al (2).…”

“…Canine mammary gland tumor (CMT) is one of the most common tumors in intact female dogs and is a therapeutic challenge due to its metastatic rate (1). In a One Health perspective, CMT was considered a spontaneous model for studying human breast cancer (BC) (2). Thus, studies on CMT can benefit both humans and dogs.…”

“…Thus, studies on CMT can benefit both humans and dogs. CMT and human BC share many clinical and pathological similarities, including hormonal regulation (2). To grow and metastasize, tumor cells require a sufficient supply of nutrients and oxygen (3).…”

“…Among angiogenic factors, vascular endothelial growth factor-A (VEGF-A) overexpression and its receptor (VEGFR-2) play key roles (3,4). VEGF-A/VEGFR-2 deregulation was previously demonstrated in canine CMT (2) and human BC (5).…”

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines with Vasculogenic Mimicry Ability <em>in vitro</em> and <em>in vivo</em>

“…3,3'-Diaminobenzidine (DAB) (EnVision, FLEX, High pH, Dako, Agilent Technologies, Santa Clara, CA, USA) was used as a chromogen and tissue counterstaining was performed with Harris Haematoxylin. Positive [19] and negative [20] controls were performed according to the previous literature.…”