Oncology

Loophole for cancer cells

Many cancers only become a mortal danger if they form metastases elsewhere in the body. Such secondary tumours are formed when individual cells break away from the main tumour and travel through the bloodstream to distant areas of the body. To do so, they have to pass through the walls of small blood vessels. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and Goethe University Frankfurt have now shown that tumour cells kill specific cells in the vascular wall. This enables them to leave the vessels and establish metastases, a process facilitated by a molecule called DR6.

This is a diagram of the mechanism by which metastatic cancer cells exit blood...
This is a diagram of the mechanism by which metastatic cancer cells exit blood vessels. The APP molecule on cancer cells activates the DR6 receptor on vascular wall cells (endothelial cells). As a result, the endothelial cell is selectively killed (through a process called necroptosis). In this way, the cancer cell creates an escape route from the bloodstream. It then either slips directly through the resulting gap (1) or interferes with chemical messengers from neighboring cells around the dead endothelial cell, causing a gap to form between them (2).
Source: MPI for Heart and Lung Research

The most common cause of cancer deaths is not the primary tumour itself but metastases that subsequently form. Most tumour cells spread via the bloodstream. To do so, individual tumour cells have to enter blood vessels and leave the bloodstream again at remote locations.

Together with scientists at the universities of Cologne and Heidelberg, the Research Group led by Stefan Offermanns, Director of the Department of Pharmacology at the Max Planck Institute for Heart and Lung Research and professor at Goethe University Frankfurt, has now succeeded in clarifying the underlying mechanism. The researchers, working with cell cultures, first observed how individual tumour cells kill specific cells in the vascular wall, called endothelial cells. This process, known as necroptosis, enabled cancer cells to overcome an endothelial cell layer in the laboratory. "We were then able to show in studies on mice that the same process occurs in living organisms," says Boris Strilic, first author of the study.

The scientists also found that endothelial cells themselves give the signal for their own death: To do this, the vascular wall cells have a receptor molecule called Death Receptor 6 (DR6) on their surface. "When a cancer cell comes into contact with it, a protein on the cell's surface, known as APP, activates DR6. This marks the start of the cancer cells' attack on the vascular wall, which culminates in the necroptosis of wall cells," Strilic explains.

Death Receptor in the cell membrane

The Max Planck researchers then showed that less necroptosis of endothelial cells and less metastasis occur in genetically modified animals in which Death Receptor 6 is disabled. "This effect was also found after a blockade of DR6 or the cancer-cell protein APP, thus confirming our previous observations," Strilic says.

It is still not entirely clear whether the cancer cells migrate directly through the resulting gap in the vascular wall or whether there is an indirect effect: "We have evidence that many more molecules are released when the vascular wall cell dies and that they render the surrounding area more permeable to cancer cells," says Offermanns.

"This mechanism could be a promising starting point for treatments to prevent the formation of metastases," says Offermanns. First, however, it must be determined whether a blockade of DR6 triggers unwanted side effects. It must also be determined to what extent the observations can be transferred to humans.


Publication:
Strilic B, Yang L, Albarrán-Juárez J, Wachsmuth L, Han K, Müller UC, Pasparakis M, Offermanns S (2016) Tumor cell-induced endothelial necroptosis via death receptor 6 promotes metastasis. Nature; 3 August, 2016

Source: MPI for Heart and Lung Research

25.08.2016

Read all latest stories

Related articles

Photo

News • Oncology

New blood test identifies if a patient has cancer

Researchers outline a new minimally invasive and inexpensive blood test that can identify cancer in patients with non-specific symptoms and whether these cancers have metastasised in the body.

Photo

News • Oncology

A clue to where cancer metastases are born

Even in remission, cancer looms. Former cancer patients and their doctors are always on alert for metastatic tumors. Now scientists at The Scripps Research Institute (TSRI) have discovered why some…

Photo

News •

Blood vessel lining cells control metastasis

Scientists from the German Cancer Research Center in Heidelberg and from the Medical Faculty Mannheim of Heidelberg University treated mice with a combination of a low-dose metronomic chemotherapy…

Related products

Mindray – BC-6800Plus Auto Hematology Analyzer

Blood Cell Couner

Mindray – BC-6800Plus Auto Hematology Analyzer

Shenzhen Mindray Bio-Medical Electronics Co., Ltd
MolGen – PurePrep 96

Extraction

MolGen – PurePrep 96

MolGen
Alsachim - Dosimmune immunosupressant Alsachim – kit (CE-IVD or RUO)

Clinical Chemistry

Alsachim - Dosimmune immunosupressant Alsachim – kit (CE-IVD or RUO)

Alsachim, a Shimadzu Group Company
Alsachim – Dosinaco anticoagulant reagent kit (RUO)

Clinical Chemistry

Alsachim – Dosinaco anticoagulant reagent kit (RUO)

Alsachim, a Shimadzu Group Company
ASP Lab Automation – Bench-top Decapper DeCap Pro

Sample Processing

ASP Lab Automation – Bench-top Decapper DeCap Pro

ASP Lab Automation AG
Subscribe to Newsletter