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Oncogene ; 36(49): 6749-6761, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-28825725

RESUMO

Within the tumor, malignant and stromal cells support each other by secreting a wide variety of growth factors and cytokines, allowing tumor growth and disease progression. The identification and regulation of those key factors in this crosstalk has opened the opportunity to develop new therapeutic strategies that not only act on the tumor cells but also on the stroma. Among these factors, S100A7 protein has gained interest in the last years. With key roles in cell motility its expression correlates with increased tumor growth, angiogenesis and metastatic potential. This work aims to deepen in the role played by extracellular S100A7 in the tumor microenvironment, offering a new integrative insight of its mechanism of action on each cellular compartment (tumor, endothelial, immune and fibroblast). As a result, we demonstrate its implication in cell migration and invasion, and its important contribution to the formation of a proinflammatory and proangiogenic environment that favors tumor progression and metastasis. Furthermore, we define its possible role in the pre-metastatic niche formation. Considering the relevance of S100A7 in cancer progression, we have developed neutralizing monoclonal antibodies, reporting for the first time the proof of principle of this promising therapeutic strategy for cancer treatment.


Assuntos
Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Proteína A7 Ligante de Cálcio S100/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Proteínas Recombinantes/farmacologia , Proteína A7 Ligante de Cálcio S100/genética , Proteína A7 Ligante de Cálcio S100/imunologia , Microambiente Tumoral/efeitos dos fármacos
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