Tumour‐associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours

Abstract

Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.

A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

“…Some studies from veterinary oncology report that in canine mammary tumors proinflammatory mediators produced by the tumor-infiltrated inflammatory cells correlate with progression and angiogenesis [20, 52–54]. In accordance, we show in dog mammary tumors a positive association between infiltrating CD3 + T-cells, VEGF, and microvessel density, implying that CD3 + T-lymphocyte cytokines in this type of cancer may stimulate angiogenesis through the induction of the proangiogenic VEGF.…”

“…Similarly to human breast cancer, in canine mammary cancer the macrophages also polarize toward the M2 phenotype [57]. Recently, we and others demonstrated that TAM infiltration is significantly associated with VEGF expression in malignant canine mammary tumors and that genes involved in angiogenic cellular pathways have been significantly upregulated in macrophages cocultured with canine mammary tumor cell lines [20, 58]. …”

“…Evidences from clinical and experimental studies indicate that macrophages are versatile cells that are capable of displaying different functional activities in order to promote breast cancer progression and metastasis [20, 120, 121]. TAMs polarization in mammary tumor sites are modulated by the tumor microenvironment and these cells are “educated” adopting a role that facilitates angiogenesis, matrix breakdown, and tumor cell motility in a COX-2-dependent manner [71, 105].…”

High COX‐2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study

“…The number expressed for CD3+ T-lymphocytes and for tumour-associated macrophages (TAMs) represents the mean value ± standard error of mean following a methodology previously used. 31,33…”

Avaliação de macrófagos e eosinófilos associados ao tumor como fatores prognósticos em mastocitomas cutâneos caninos

“…Os dados encontrados em literatura quanto a expressão de TAM e de eosinófilos, bem como a sua participação na angiogênese tumoral e progressão tumoral são conflitantes (LEEK et al, 1996;TAKANAMI et al 2002;TATAROGLU et al 2004;TSUTSUI et al, 2005;UTRERA-BARILLAS et al, 2010;KROL et al, 2011;GOLLAPUDI et al, 2013;RAPOSO et al, 2013;SUYANI et al, 2013;YURI et al, 2014). Além da análise dos TAMs, a adição de outros parâmetros como a análise de expressão VEGF e densidade microvascular, poderia auxiliar na investigação do envolvimento dos macrófagos ao processo de vasculogênese.…”