Navigation Links
How cancer spreads by aggregating platelets
Date:8/30/2007

BETHESDA, Md. Scientists have provided new details about how cancer cells spread by surrounding themselves with platelets the blood cells needed for blood clotting. Katsue Suzuki-Inoue, Associate Professor of Medicine at the University of Yamanashi, Japan, and colleagues have identified for the first time a protein on the surface of platelets that plays a key role in cancer-induced platelet aggregation. These results could help design new drugs that prevent cancer cells from metastasizing, or spreading throughout the body.

In order to spread, cancer cells release chemicals that make neighboring platelets aggregate and surround the cancer cells, helping them evade the immune system and allowing them to bind to the blood vessels inner linings, Suzuki-Inoue says. We have discovered how one of these chemicals, called podoplanin, binds to the platelet cells and stimulate their aggregation. Although podoplanin has been known since 1990, how it induces platelet cell aggregation has been a mystery until now.

The new study, to be published in the September 7 issue of the Journal of Biological Chemistry, was selected as a Paper of the Week by the journals editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Suzuki-Inoue and colleagues had previously discovered that the snake venom rhodocytin stimulates platelet aggregation by binding to a protein called C-type lectin-like receptor 2 (CLEC-2) located on the surface of the platelets in a way similar to a key (rhodocytin) binding to a lock (CLEC-2).

By studying the details of what happens inside these platelets before and during aggregation, the scientists noticed many similarities with the way platelets aggregate when they are induced by podoplanin from cancer cells. Whether stimulated by rhodocytin or podoplanin, the platelets are slow to aggregate at first and, after they start aggregating, the proteins that are activated inside the platelets are similar in both cases.

Suzuki-Inoue and her team reasoned that maybe CLEC-2 binds not only to rhodocytin but also to podoplanin. The scientists tested this hypothesis by first growing CLEC-2 in culture and then by adding them to cultured cells expressing podoplanin. The hypothesis was confirmed: CLEC-2 and podoplanin bound to each other in the same lock-and-key mechanism displayed by CLEC-2 and rhodocytin.

We were pleasantly surprised, Suzuki-Inuoue says. After all these years, we finally found the long-missing protein to which podoplanin binds to promote platelet aggregation.

The scientists confirmed their findings by mixing podoplanin-expressing cells with platelet cells genetically altered so that the CLEC-2 on their surface could not bind to podoplanin. Platelet aggregation was completely inhibited, confirming that CLEC-2 was the protein necessary for podoplanin-induced platelet aggregation.

This result also suggested that it may be possible to prevent cancer cells from stimulating platelet aggregation and thus allow the cancer cells to metastasize by blocking the interaction between CLEC-2 and podoplanin.

Our study clearly shows that podoplanin on the surface of tumor cells induces platelet aggregation by interacting with CLEC-2 on the surface of platelet cells, Suzuki-Inuoue says. Preventing CLEC-2 and podoplanin from binding to each other may be a good therapeutic way of preventing tumor metastasis.

The role of podoplanin-CLEC-2 interaction may not be limited to tumor metastasis, the scientists note. When podoplanin and CLEC-2 bind to each other, not only do platelets aggregate, but they also release chemicals that may form new blood vessels which, in turn, provide the tumor with the nutrients and oxygen it needs to grow. As a result, locking the podoplanin-CLEC-2 interaction may not only prevent cancer metastasis but also limit the growth of cancer cells, Suzuki-Inuoue says.

The researchers also found that podoplanin present within lymphatic vessels which carry plasma and white blood cells also induces platelet aggregation, showing that a better understanding of how podoplanin and CLEC-2 bind together may provide information on how lymphatic vessels form and work.

Suzuki-Inuoue and colleagues are now trying to develop antibodies that look like CLEC-2 and that can bind to podoplanin, preventing it from attaching to platelet cells. The scientists are also investigating the role of the podoplanin-CLEC-2 interaction in the formation of blood clots and the development of lymphatic vessels.


'/>"/>
Contact: Pat Pages
ppages@asbmb.org
301-634-7366
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

Related biology news :

1. Viral DNA sequence a possible trigger for breast cancer
2. Adding Radiation Therapy To Chemotherapy Improves Survival In Patients With High-risk Breast Cancer
3. Jump-starting T Cells In Skin Cancer
4. Deficient DNA Repair Capacity Associated With Increased Risk Of Breast Cancer
5. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
6. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
7. Columbia research lifts major hurdle to gene therapy for cancer
8. Fox Chase Cancer Center scientists identify immune-system mutation
9. Combination therapy boosts effectiveness of telomere-directed cancer cell death
10. Breakthrough Microarray-based Technology for the Study of Cancer
11. Mitochondrial DNA mutations play significant role in prostate cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/6/2017)... , Jan. 6, 2017  Privately-held CalciMedica, Inc., ... in healthy volunteers of a novel calcium release-activated ... acute pancreatitis. Acute pancreatitis, sudden ... mild disorder, but can be very serious.  In severe ... sepsis, where extended hospital stays, time in the ...
(Date:1/4/2017)... 2017  CES 2017 – Valencell , the ... announced the launch of two new versions of ... biometric sensor modules that incorporate the best of ... expertise. The two new designs include Benchmark BE2.0, ... and Benchmark BW2.0, a 2-LED version of its ...
(Date:12/20/2016)... LONDON , Dec. 20, 2016 ... car sharing, rental and leasing is stoking significant ... of radio frequency technology, Bluetooth low energy (BLE), ... emerge as the next wave of wireless technologies ... vehicle access system to advanced access systems opens ...
Breaking Biology News(10 mins):
(Date:1/14/2017)... 13, 2017  The Alliance for Safe Biologic Medicines ... FDA final guidance on biologic naming: ... in emphasizing the importance of distinct naming for all ... the benefits biosimilars will bring to patients, including new ... the portion of the Guidance dealing with suffix design ...
(Date:1/13/2017)... ... 13, 2017 , ... Two Kalamazoo entrepreneurs have launched AgTonik ... that farms, greenhouses and hydroponics operations use to increase yields and promote plant ... segments of customers using this high grade fulvic acid extracted from a mineral ...
(Date:1/12/2017)... ... January 12, 2017 , ... ... IS A SUCCESS , VTI, Vertebral Technologies, Inc., announces the successful outcome ... expandable device. Since September 2016, VTI (Vertebral Technologies, Inc.) has partnered with ...
(Date:1/12/2017)... ... 2017 , ... Huffman Engineering, Inc. , a leader in control systems ... company’s Lincoln office as a chemical engineer. In his new role, Beck will ... the life science manufacturing and water/wastewater industries. , Prior to joining Huffman Engineering, Beck ...
Breaking Biology Technology: