| GeneLibs

题目:: Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.
作者:: Nakamura(Koji),Sawada(Kenjiro),Kinose(Yasuto),Yoshimura(Akihiko),Toda(Aska),Nakatsuka(Erika),Hashimoto(Kae),Mabuchi(Seiji),Morishige(Ken-Ichirou),Kurachi(Hirohisa),Lengyel(Ernst),Kimura(Tadashi)
状态:: 发布时间2016-10-19 , 更新时间 2016-10-21
期刊:: Mol Cancer Res
摘要:: Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMCs) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications are exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and co-cultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein found to be enriched in the cancer cell derived exosomes, transferred and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, while CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion.,Mechanistic insight from the current study suggests therapeutic targeting of exosomes may be beneficial in treating ovarian cancer.
语言:: eng
DOI:: 10.1158/1541-7786.MCR-16-0191

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息