期刊
CELLS
卷 11, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/cells11162474
关键词
cancer; CD9; Fab; cell morphology; migration; colon carcinoma; extracellular vesicle
类别
资金
- NIH [R15CA252990]
Intercellular communication between cancer cells and healthy cells in the tumor microenvironment plays a crucial role in cancer progression and metastasis. Extracellular vesicles (EVs) have emerged as novel mediators in this communication. In this study, the researchers developed a monovalent Fab fragment antibody targeting CD9 tetraspanin and demonstrated its effectiveness in blocking the internalization of melanoma cell-derived EVs and the transfer of their cargo proteins. The study also showed the potential of this anti-CD9 Fab antibody in inhibiting the phenotypic transformation and migration of colorectal cancer cells. Intercepting EV-mediated communication in the tumor niche with this antibody could lead to new anti-cancer therapeutic strategies.
Intercellular communication between cancer cells themselves or with healthy cells in the tumor microenvironment and/or pre-metastatic sites plays an important role in cancer progression and metastasis. In addition to ligand-receptor signaling complexes, extracellular vesicles (EVs) are emerging as novel mediators of intercellular communication both in tissue homeostasis and in diseases such as cancer. EV-mediated transfer of molecular activities impacting morphological features and cell motility from highly metastatic SW620 cells to non-metastatic SW480 cells is a good in vitro example to illustrate the increased malignancy of colorectal cancer leading to its transformation and aggressive behavior. In an attempt to intercept the intercellular communication promoted by EVs, we recently developed a monovalent Fab fragment antibody directed against human CD9 tetraspanin and showed its effectiveness in blocking the internalization of melanoma cell-derived EVs and the nuclear transfer of their cargo proteins into recipient cells. Here, we employed the SW480/SW620 model to investigate the anti-cancer potential of the anti-CD9 Fab antibody. We first demonstrated that most EVs derived from SW620 cells contain CD9, making them potential targets. We then found that the anti-CD9 Fab antibody, but not the corresponding divalent antibody, prevented internalization of EVs from SW620 cells into SW480 cells, thereby inhibiting their phenotypic transformation, i.e., the change from a mesenchymal-like morphology to a rounded amoeboid-like shape with membrane blebbing, and thus preventing increased cell migration. Intercepting EV-mediated intercellular communication in the tumor niche with an anti-CD9 Fab antibody, combined with direct targeting of cancer cells, could lead to the development of new anti-cancer therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据