Background: Osteosarcomas, the second most prevalent primary malignancy of the bone, are often presented with high-grade subclinical metastatic disease that metastasizes at very early stages. Exosomes, as molecular information carriers, may play a potent role in the occurrence and development of tumors through oncogenic molecular reprogramming of tumor-associated macrophage (TAM). In this study, we will investigate the effect of osteosarcoma-derived exosomes on the polarization of TAM and decipher its underlying molecular mechanism. Material and Methods: Osteosarcoma-derived exosomes from MG63 cells were isolated and characterized by transmission electron microscopy, and nano-particle size analysis. Double uorescence staining was performed to con rm the macrophages phagocytosis of exosomes. Western blot, qRT-PCR, and transwell assays were conducted to assess the effect of exosomes on migration, invasion, and macrophage differentiation. The mouse model of osteosarcoma was established to evaluate the effects of exosomes on lung metastasis in vivo. Results: MG63 exosomes were successfully isolated and veri ed to be phagocytized by macrophages through uorescence confocal microscopy. The results revealed that osteosarcoma cells could induce M2 type differentiation of macrophages largely through Tim-3 mediated by exosomes, which in turn could promote the migration, invasion, EMT, and lung metastasis of osteosarcoma cells through the secretion of cytokines including IL-10, TGFβ, and VEGF. Conclusions: Our results demonstrated that osteosarcoma-derived exosomes induced M2 polarization of macrophages and promoted the invasion and metastasis of tumors through Tim-3; besides, the study also suggests a novel therapeutic target for future studies.
Background: Osteosarcomas, the second most prevalent primary malignancy of the bone, are often presented with high-grade subclinical metastatic disease that metastasizes at very early stages. Exosomes, as molecular information carriers, may play a potent role in the occurrence and development of tumors through oncogenic molecular reprogramming of tumor-associated macrophage (TAM). In this study, we will investigate the effect of osteosarcoma-derived exosomes on the polarization of TAM and decipher its underlying molecular mechanism. Material and Methods: Osteosarcoma-derived exosomes from MG63 cells were isolated and characterized by transmission electron microscopy, and nano-particle size analysis. Double fluorescence staining was performed to confirm the macrophages phagocytosis of exosomes. Western blot, qRT-PCR, and transwell assays were conducted to assess the effect of exosomes on migration, invasion, and macrophage differentiation. The mouse model of osteosarcoma was established to evaluate the effects of exosomes on lung metastasis in vivo. Results: MG63 exosomes were successfully isolated and verified to be phagocytized by macrophages through fluorescence confocal microscopy. The results revealed that osteosarcoma cells could induce M2 type differentiation of macrophages largely through Tim-3 mediated by exosomes, which in turn could promote the migration, invasion, EMT, and lung metastasis of osteosarcoma cells through the secretion of cytokines including IL-10, TGFβ, and VEGF. Conclusions: Our results demonstrated that osteosarcoma-derived exosomes induced M2 polarization of macrophages and promoted the invasion and metastasis of tumors through Tim-3; besides, the study also suggests a novel therapeutic target for future studies.
Background: Neuroendocrine carcinoma (NEC) of the esophagus is rare, highly aggressive and lacks biological features. Case presentation: In this report, we describe a patient with Esophageal NEC who was successfully treated using endoscopic submucosal dissection (ESD). A 55-year-old woman presented with intermittent mild dysphagia for 2 months. Gastroscopy revealed a disc-shaped protruding lesion about 18mm×18mm in size on the upper esophagus, 25cm from the incisors. Endoscopic ultrasonography (EUS) demonstrated the bulged lesion was highly echoic and homogeneous, originating from the muscularis mucosa. We assessed en bloc resection by ESD for therapeutic diagnosis to be a safe and appropriate treatment. The tumor was removed using ESD. Histopathological examination revealed a poorly differentiated neoplasm comprising large cells with marked nuclear atypia and multifocal necrosis Immunohistochemistry staining revealed tumor tissue that was positive for Ki67, CgA, Syn, CD56, but negative for P40, P63, S-100 protein. These histopathological results were consistent with a diagnosis of esophageal NEC, large cell type, derived from the muscularis mucosae. After comprehensive consideration, we adopted the combination treatments (ESD plus an adjuvant chemotherapy). The patient has been followed up till now with no recurrence. Conclusions: En bloc resection approach by ESD play a vital role in the early therapeutic diagnosis of esophageal NEC.
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