RESUMO
Metastasis is driven by extensive cooperation between a tumor and its microenvironment, resulting in the adaptation of molecular mechanisms that evade the immune system and enable pre-metastatic niche (PMN) formation. Little is known of the tumor-intrinsic factors that regulate these mechanisms. Here we show that expression of the transcription factor interferon regulatory factor 5 (IRF5) in osteosarcoma (OS) and breast carcinoma (BC) clinically correlates with prolonged survival and decreased secretion of tumor-derived extracellular vesicles (t-dEVs). Conversely, loss of intra-tumoral IRF5 establishes a PMN that supports metastasis. Mechanistically, IRF5-positive tumor cells retain IRF5 transcripts within t-dEVs that contribute to altered composition, secretion, and trafficking of t-dEVs to sites of metastasis. Upon whole-body pre-conditioning with t-dEVs from IRF5-high or -low OS and BC cells, we found increased lung metastatic colonization that replicated findings from orthotopically implanted cancer cells. Collectively, our findings uncover a new role for IRF5 in cancer metastasis through its regulation of t-dEV programming of the PMN.
Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Fatores Reguladores de Interferon , Metástase Neoplásica , Microambiente Tumoral , Vesículas Extracelulares/metabolismo , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Osteossarcoma/patologia , Osteossarcoma/genética , Osteossarcoma/metabolismo , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Pneumomediastinum is a relatively uncommon occurrence in pediatric patients. After mediastinal air leak, air may dissect through a variety of tissue planes within the chest, neck, and abdomen. We report the case of a 16-year-old adolescent boy who presented with spontaneous pneumomediastinum accompanied by the presence of air within the spinal canal. We suggest use of the term "spontaneous pneumorrhachis" to distinguish this type of presentation from other potential causes.