First Author | Razzo BM | Year | 2020 |
Journal | Carcinogenesis | Volume | 41 |
Issue | 5 | Pages | 625-633 |
PubMed ID | 31245809 | Mgi Jnum | J:290637 |
Mgi Id | MGI:6441667 | Doi | 10.1093/carcin/bgz124 |
Citation | Razzo BM, et al. (2020) Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma. Carcinogenesis 41(5):625-633 |
abstractText | Circulating tumor-derived exosomes (TEX) interact with a variety of cells in cancer-bearing hosts, leading to cellular reprogramming which promotes disease progression. To study TEX effects on the development of solid tumors, immunosuppressive exosomes carrying PD-L1 and FasL were isolated from supernatants of murine or human HNSCC cell lines. TEX were delivered (IV) to immunocompetent C57BL/6 mice bearing premalignant oral/esophageal lesions induced by the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Progression of the premalignant oropharyngeal lesions to malignant tumors was monitored. A single TEX injection increased the number of developing tumors (6.2 versus 3.2 in control mice injected with phosphate-buffered saline; P < 0.0002) and overall tumor burden per mouse (P < 0.037). The numbers of CD4+ and CD8+ T lymphocytes infiltrating the developing tumors were coordinately reduced (P < 0.01) in mice injected with SCCVII-derived TEX relative to controls. Notably, TEX isolated from mouse or human tumors had similar effects on tumor development and immune cells. A single IV injection of TEX was sufficient to condition mice harboring premalignant OSCC lesions for accelerated tumor progression in concert with reduced immune cell migration to the tumor. |