RESUMO
Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Macrófagos , RNA Circular , Microambiente Tumoral , Animais , Humanos , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Exossomos/metabolismo , Exossomos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , Metástase Neoplásica/genética , RNA Circular/genética , RNA Circular/metabolismo , Microambiente Tumoral/genética , Camundongos NusRESUMO
Adenomatoid tumor (AT) is an extremely rare benign tumor in the testis of infants. A case of 14-month-old boy with testicular adenomatoid tumor was reported in this study. On physical examination, a smooth solid nodule sized 8 mm could be palpated with little tenderness on the head of the right testis. It could be clearly revealed by B ultrasonic scanning and computerized tomography. The patient underwent right radical orchiectomy. In postoperative histopathological study, the tumor was characterized by diffuse sheets of epithelioid cell and desmo-stroma structures. There was positive immunohistochemical staining of mesothelioma-associated antigens. The tumor should be differentiated from the tumor of the male genital tract including benign and malignant tumors of both epithelial and stromal origin. And we followed the case and no nodule was found in his scrotum by physical examination and scrotal ultrasonography after 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 months. These findings have important implications that the histogenesis of adenomatoid tumor of the testis is unclear yet. The diagnosis depends on pathologic studies, and should be differentiated from paratesticular malignant mesothelioma and sclerosed lipogranuloma. Radical surgery is the common choice, and as a result of getting a good prognosis.