Gateway for metastases

July 03, 2013

Malignant tumours often spread to remote areas of the body. In the majority of cases, metastases formation develops via the blood vascular system. The blood platelets thereby provide invaluable help to the tumour cells in penetrating new organs. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have identified the P2Y2 receptor molecule on the cells of the blood platelet wall as the gateway that allows the cancer cells to enter the organs. They now aim to prevent the formation of metastases through the targeted blocking of this key molecule.

Blood platelets play a crucial role in haemostasis. When a blood vessel is injured, the platelets ensure the rapid initial closure of the wound. To do this, they quickly adhere to the wall of the injured blood vessel, thereby attracting more platelets which aggregate and form a plug that blocks the opening in the blood vessel wall. To enable the optimal functioning of this "rapid reaction force" in the event of injury to blood vessel walls, the blood platelets release a veritable shower of signal molecules. The cells communicate with each other in this manner. Moreover, the platelets, which normally circulate in the blood stream in an inactive state, are activated in a matter of seconds and fundamentally alter their characteristics.

Malignant tumours, which often spread to previously unaffected organs through the blood stream, use the blood platelets to penetrate the hermetically-sealed blood vessel wall. "It has long been known that metastasising tumour cells are capable of establishing close contact with blood platelets and activating them. Animal experiments have shown that tumour cells form far fewer metastases in the absence of blood platelets," says Stefan Offermanns, Director of the Department of Pharmacology at the Bad Nauheim-based Max Planck Institute. In addition, clinical studies have shown that patients who receive long-term treatment with platelet inhibitors like acetylsalicylic acid present a lower risk of developing metastasising tumours.

Offermanns' Research Group has succeeded in explaining exactly how this process unfolds. Activated blood cells release a large amount of molecules including adenosine triphosphate (ATP). The scientists observed in cell cultures that blocking ATP release from blood platelets resulted in a significant reduction in the number of tumour cells migrating through the endothelial cells in the blood vessel wall. "We succeeded in demonstrating the same phenomenon in experiments on mice, in which the release of ATP from blood platelets was blocked. In this case too, far fewer tumour cells slipped through the endothelial barrier and fewer metastases formed," says Dagmar Schuhmacher, one of the study's first authors.

However, what exactly happens in the blood vessel wall that enables the tumour cells to penetrate it? The Max Planck researchers were able to demonstrate that ATP from the blood platelets binds with a particular receptor called P2Y2. This docking site is located on the surface of the endothelial cells. "When ATP binds to these receptors, small openings form between the individual endothelial cells. The tumour cells exit the blood vessel through these openings and migrate into the organ," explains Boris Strilic, also a first author of the study.

With the identification of this hitherto unknown role of blood platelets in metastases formation, the researchers hope to have found possible starting points for a new therapeutic approach. "We will now test whether specific blockers for the P2Y2 receptor or substances that inhibit the release of ATP from blood platelets can suppress tumour cell metastasis in different animal models," says Offermanns. The specific challenge the scientists must overcome here is to avoid suppressing the actual job of the platelets, namely haemostasis, in the process. If they manage to do this, a better treatment for malignant tumours may become available in the future.
-end-
Original publication:

Dagmar Schumacher, Boris Strilic, Kishor Kumar Sivaraj, Nina Wettschureck, Stefan Offermanns: Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2-receptor. Cancer Cell (2013), http://dx.doi.org/10.1016/j.ccr.2013.05.008

Max-Planck-Gesellschaft

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.