AUTHOR=dos Reis Diego Carlos , Damasceno Karine Araújo , de Campos Cecília Bonolo , Veloso Emerson Soares , Pêgas Gabriela Rafaela Arantes , Kraemer Lucas Rocha , Rodrigues Michele Angela , Mattos Matheus Silvério , Gomes Dawidson Assis , Campos Paula Peixoto , Ferreira Enio , Russo Remo Castro , Cassali Geovanni Dantas TITLE=Versican and Tumor-Associated Macrophages Promotes Tumor Progression and Metastasis in Canine and Murine Models of Breast Carcinoma JOURNAL=Frontiers in Oncology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00577 DOI=10.3389/fonc.2019.00577 ISSN=2234-943X ABSTRACT=

Versican and tumor-associated macrophages (TAMs) are involved in growth and metastases in several cancers. Here, we investigated the potential role of versican, a matrix proteoglycan, and its correlation with TAMs infiltrates in different stages of two different breast cancer models: spontaneous canine mammary gland carcinomas and the murine 4T1 breast cancer model. The stromal versican expression was correlated with TAMs accumulation in tumors with an advanced stage from spontaneous canine mammary carcinoma samples. Versican expression in mice, identified in late stages of tumor progression, was associated to a high number of peri-tumoral infiltrating TAMs. Indeed, TAMs were related to a pro-inflammatory and pro-angiogenic state in the primary tumor. Furthermore, TAMs accumulation was related to versican expression in the lungs and an increased number of pulmonary metastatic nodules with pulmonary mechanical dysfunction, which was due to leukocyte influx in the airways and elevated growth factor levels in the microenvironment. Thus, we suggest that versican and TAMs as attractive targets for breast cancer therapy.