Personalized Medicine Laboratory, National Institute of Gastroenterology "S. De Bellis", Via Turi 27, Castellana Grotte, 70013 Bari, Italy.
Institute for Chemical and Physical Processes (IPCF)-CNR SS Bari, Via Orabona 4, 70126 Bari, Italy.
Cells. 2019 Jul 25;8(8):777. doi: 10.3390/cells8080777.
Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation, and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of the gastroenteric tract. Here, a still unknown role of Frizzled 10 (FZD10) protein was identified. In particular, the presence of FZD10 and FZD10-mRNA in exosomes extracted from culture medium of the untreated colorectal, gastric, hepatic, and cholangio cancer cell lines, was detected. A substantial reduction in the FZD10 and FZD10-mRNA level was achieved in FZD10-mRNA silenced cells and in their corresponding exosomes. Concomitantly, a significant decrease in viability of the silenced cells compared to their respective controls was observed. Notably, the incubation of silenced cells with the exosomes extracted from culture medium of the same untreated cells promoted the restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization.
细胞外囊泡 (EVs) 在癌变过程中参与细胞间通讯,癌细胞能够分泌 EVs,特别是包含分子的外泌体,可以转移到受体细胞中,诱导病理过程和显著的改变,如转移、增殖增加和癌变演变。FZD 蛋白是 Wnt 信号通路中的受体家族,在胃肠道的癌变中发挥重要作用。在这里,鉴定了 Frizzled 10 (FZD10) 蛋白的一个未知作用。特别是,在未经处理的结直肠、胃、肝和胆管癌细胞系培养物中提取的外泌体中检测到 FZD10 和 FZD10-mRNA 的存在。在 FZD10-mRNA 沉默的细胞及其相应的外泌体中,FZD10 和 FZD10-mRNA 水平显著降低。同时,与各自的对照相比,沉默细胞的活力显著降低。值得注意的是,将沉默细胞与来自相同未经处理细胞培养物的外泌体孵育可促进细胞活力的恢复,以及 FZD10 和 FZD10-mRNA 水平的恢复,这表明 FZD10 和 FZD10-mRNA 传递的外泌体可能是癌症再激活的潜在信使,并在远距离转移中发挥积极作用。