Exosomes in HNSCC Progression

胞外体是由多泡分泌的小胞外小泡。 内切体(MVE)和最近被认为促进癌症转移。 胞外体携带有生物活性的蛋白质、脂类和核酸，是一种重要但很差的 了解肿瘤微环境的组成。我们最近发现富含肌动蛋白 被称为invadoodia的侵袭性结构是MVE在癌细胞中的关键对接位置，导致 外周小体分泌增强。此外，我们还发现，关键的跨足类调节因子 Cortactin促进MVE对接和外体分泌。值得注意的是，皮质蛋白是基因扩增的。 在许多癌症中过表达，特别是在头颈部鳞状细胞中 癌症(HNSCC)。此外，HNSCC中皮质素的过度表达与 患者存活率降低，转移率增加。根据这些数据，我们假设 皮质蛋白的过度表达导致HNSCC预后不良，因为它在 促进外切体分泌。此外，我们假设关键的外显体货物 与Cortactin协同促进肿瘤诱导的血管生成，淋巴管生成， 和转移。具体地说，我们已经确定EphB-ewitinB信号是一个关键的血管生成信号 由HNSCC分泌的外切体调节的轴。因此，我们建议数字和 外切体的分子货物以协同的方式驱动侵袭性的HNSCC行为。我们 将检验这些假设，并利用我们的工作来识别潜在的胞外体血--和 区域和远处转移的基于组织的生物标记物。

Exosomes are small extracellular vesicles (EVs) that are secreted from multivesicular endosomes (MVE) and have been recently recognized to promote cancer metastasis. Exosomes carry bioactive proteins, lipids and nucleic acids and are an important but poorly understood component of the tumor microenvironment. We recently discovered that actin-rich invasive structures called invadopodia are key docking sites for MVE in cancer cells, leading to enhanced exosome secretion. Furthermore, we found that the key invadopodia regulator cortactin enhances MVE docking and exosome secretion. Notably, cortactin is gene amplified and overexpressed in a number of cancers, especially in head and neck squamous cell carcinoma (HNSCC). Furthermore, cortactin overexpression in HNSCC is correlated with decreased patient survival and increased metastasis. Based on these data, we hypothesize that cortactin overexpression drives poor prognosis in HNSCC due to its key role in promoting exosome secretion. Furthermore, we hypothesize that key exosome cargoes synergize with cortactin to promote tumor-induced angiogenesis, lymphangiogenesis, and metastasis. Specifically, we have identified EphB-ephrinB signaling as a key angiogenic axis regulated by HNSCC-secreted exosomes. Thus, we propose that both the number and molecular cargo of exosomes drive aggressive HNSCC behavior in a synergistic manner. We will test these hypotheses and leverage our work to identify potential exosomal blood-and tissue-based biomarkers of regional and distant metastasis.