Identification of PTPRZ as a drug target for cancer stem cells in glioblastoma

July 19, 2017, National Institutes of Natural Sciences
The left and right show xenograft tumors of parental cells and PTPRZ knockdown cells, respectively. Credit: NIBB

Glioblastoma is a malignant brain tumor with high mortality. Cancer stem cells are thought to be crucial for tumor initiation and its recurrence after standard therapy with radiation and temozolomide (TMZ) chemotherapy. Protein tyrosine phosphatase receptor type Z (PTPRZ) is an enzyme that is highly expressed in glioblastoma, especially in cancer stem cells.

The research group of Professor Masaharu Noda and Researcher Akihiro Fujikawa of the National Institute for Basic Biology (NIBB) showed that the enzymatic activity of PTPRZ is requisite for the maintenance of stem cell properties and tumorigenicity in glioblastoma cells.

PTPRZ knockdown strongly inhibited tumor growth of C6 glioblastoma cells in a mouse xenograft model. In addition, the research team discovered NAZ2329, an allosteric inhibitor of PTPRZ, efficiently suppressed stem cell-like properties of in culture, and tumor growth in C6 glioblastoma xenografts. These results indicate that pharmacological inhibition of PTPRZ is a promising strategy for the treatment of malignant gliomas.

NAZ2329 bound to an allosteric pocket close to the active center of PTPRZ. Credit: NIBB, ASUBIO Pharma
Tumor growth was inhibited more effectively by co-treatment with NAZ2329 and TMZ than by the individual treatments. Credit: NIBB

Explore further: Using a microRNA to shift the makeup of glioblastoma subtypes

More information: Akihiro Fujikawa et al, Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells, Scientific Reports (2017). DOI: 10.1038/s41598-017-05931-8

Related Stories

Using a microRNA to shift the makeup of glioblastoma subtypes

July 13, 2017
Glioblastoma multiforme (GBM), an extremely aggressive brain cancer, is a very complex disease. It is characterized by a fast-growing tumor in the brain composed of many subpopulations of cells, including glioblastoma stem ...

PTPRZ-MET fusion protein: A new target for personalized brain cancer treatment

October 14, 2014
Researchers at the University of California, San Diego School of Medicine have identified a new fusion protein found in approximately 15 percent of secondary glioblastomas or brain tumors. The finding offers new insights ...

Brain cancer study reveals therapy clues

May 10, 2017
Researchers have pinpointed two key molecules that drive the growth of an aggressive type of adult brain cancer.

Researchers identify protein pathway involved in brain tumor stem cell growth

February 26, 2015
Glioblastomas are a highly aggressive type of brain tumor, with few effective treatment options. Moffitt Cancer Center researchers are one step closer to understanding glioblastoma development following the identification ...

Study reveals new information on how brain cancer spreads

November 17, 2016
Glioblastoma multiforme remains the most common and highly lethal brain cancer and is known for its ability to relapse. Researchers at The University of Texas MD Anderson Cancer Center have identified a pathway by which cancer ...

Combination therapy for glioblastoma shows promising results in early-stage research

January 25, 2017
UCLA researchers have discovered that combining a vaccine developed at UCLA with other experimental therapies and FDA-approved treatments shows promise for reducing the size of advanced brain tumors. The immunotherapy, which ...

Recommended for you

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Combining three treatment strategies may significantly improve melanoma treatment

December 12, 2018
A study by a team led by a Massachusetts General Hospital (MGH) investigator finds evidence that combining three advanced treatment strategies for malignant melanoma—molecular targeted therapy, immune checkpoint blockade ...

Researchers use computer model to predict prostate cancer progression

December 12, 2018
An international team of cancer researchers from Denmark and Germany have used cancer patient data to develop a computer model that can predict the progression of prostate cancer. The model is currently being implemented ...

An integrated approach to finding new treatments for breast cancer

December 12, 2018
Unraveling the complexity of cancer biology can lead to the identification new molecules involved in breast cancer and prompt new avenues for drug development. And proteogenomics, an integrated, multipronged approach, seems ...

New insight into stem cell behaviour highlights therapeutic target for cancer treatment

December 12, 2018
Research led by the University of Plymouth and Technische Universität Dresden has identified a new therapeutic target for cancer treatment and tissue regeneration – a protein called Prominin-1.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.