Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have determined one of the ways in which cancers in remission can spring back into action. This knowledge has inspired a new treatment idea designed to prevent cancer recurrence and metastasis.
Two enzymes called NE (green dots) and MMP9 (red dots) stud the scaffold of DNA NETs expelled by neutrophils, or white blood cells. These enzymes sequentially cleave a protein called laminin-111 in lung tissue, inducing a signal that causes nearby dormant cancer cells to reawaken and begin proliferating, the seed of a possible metastatic tumor.
Even after successful cancer treatment, dormant, non-dividing cancer cells that previously detached from the original tumor may still exist elsewhere in the body. If awakened, these cells can proliferate and grow into metastatic tumors. A CSHL team studying metastasis to the lungs has now identified signals accompanying inflammation that can awaken dormant cancer cells.
Whether inflammation can directly cause cancer recurrence, and if so how, has not been clear. In their new research, the team demonstrates that sustained lung inflammation, including that caused by tobacco smoke exposure, can cause dormant breast and prostate cancer cells that have traveled to the lungs to awaken and begin to divide. These cells can now form a metastasis in the lungs. Metastasis accounts for the bulk of lethality from most common cancers.
Importantly, the team, led by CSHL Associate Professor Mikala Egeblad, and including researchers from the Dana-Farber Cancer Institute and UC Davis, also demonstrate a way of blocking the signaling that awakened the dormant cancer cells, a concept that could prevent cancer recurrence or lessen its frequency.
Phó Thủ tướng Vương Đình Huệ: Bộ Công Thương hoàn thiện phương án điều chính giá điện
Wednesday November 08, 2017
Dân trí Theo tin vừa phát đi từ Bộ Tài chính chiều nay (8/11), tại cuộc họp với Ban chỉ đạo điều hành giá mới đây, Phó Thủ tướng Vương Đình Huệ đã yêu cầu Bộ Công Thương khẩn trương hoàn thiện phương án điều chỉnh giá điện. >> Giá điện sẽ tăng vô lý […]
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Egeblad’s team showed that sustained lung inflammation, caused either by exposing mice to tobacco smoke or to a component of bacteria known as endotoxin, induced common white blood cells called neutrophils to awaken nearby dormant cancer cells in an extraordinary way.
Neutrophils, which we normally rely upon to kill invaders like bacteria and yeast, have several ways of vanquishing their prey. One is to expel their DNA into the space beyond the cell membrane. Laced with toxic enzymes, this expelled DNA forms gauzy, net-like traps (called neutrophil extracellular traps, or NETs) that can kill a pathogen.
A few scattered white blood cells called neutrophils (red) are seen in normal mouse lung tissue, far left. Four hours after an agent is delivered nasally to promote lung inflammation, the number of neutrophils visibly increases, and web-like DNA ‘NETs’ (green) become visible for the first time. Neutrophils and NETs come to dominate the scene on succeeding days as the inflammatory agent is again delivered. The direct relation of inflammation and NET formation can result in the reawakening of dormant cancer cells if they are in the immediate vicinity—one mechanism of metastasis.
The new research shows that sustained lung inflammation causes the formation of NETs in the area around dormant cancer cells. Two enzymes in the NETs, called NE (neutrophil elastase) and MMP9 (matrix metalloproteinase 9), interact with a protein in tissue called laminin. In sequence, first NE then MMP9 make cuts in laminin proteins. This changes the protein’s shape, exposing a new surface, called an epitope.
This epitope, when recognized by dormant cancer cells nearby, spurs signaling that awakens the cancer cells. “The dormant cancer cells recognize that new shape of the laminin and they say, ‘we should start growing again,’” Egeblad says.
The team created an antibody to block the epitope exposed on the laminin proteins. In mice, this prevented the reawakening of dormant cancer cells nearby. Work has begun to optimize the antibody and compare it with other approaches to interfere with NETs, with the hope of eventually conducting trials in people.
The post How a sleeping cancer awakens and metastasizes appeared first on Cold Spring Harbor Laboratory.
Doanh nghiệp Việt: Cần chủ động hội nhập và hợp tác đầu tư
Tuesday November 07, 2017
Đó là chia sẻ của doanh nhân Việt Nam tiêu biểu Trần Văn Mười – Chủ tịch Tập đoàn Quốc tế Năm Sao, Chủ tịch Công ty TNHH Phân bón Quốc tế Năm Sao Campuchia về kinh nghiệm khi đầu tư ra thị trường nước ngoài trong khuôn khổ Hội nghị Thượng đỉnh kinh doanh […]
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