Navigation Links
UT Southwestern scientists make mouse model of human cancer, demonstrate cure

DALLAS March 5, 2013 UT Southwestern Medical Center scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer.

"To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor," said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study published in Cell and online. The study's first author is Dr. Wei Mo, a postdoctoral researcher in the department.

"We showed that blocking the activity of a receptor molecule named CXCR4 in these tumors through genetic manipulation or by chemical blockade inhibited tumor development. Together, these data reveal a potential target for therapy of these uncommon but currently untreatable malignant peripheral nerve sheath tumors (MPNSTs)," Dr. Parada added.

The study is a collaboration between Dr. Parada's laboratory and that of Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology. Dr. Le also is co-director of the adult Comprehensive Neurofibromatosis Clinic at UT Southwestern, the first such clinic in North Texas, which is part of the Simmons Comprehensive Cancer Center. The researchers noted that co-authors at The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, greatly accelerated the research effort.

MPNSTs are rare but highly aggressive tumors that are resistant to therapy and are typically fatal. The malignancies can occur sporadically or in a subset of patients with a condition called neurofibromatosis 1 (NF1) one of the most commonly inherited disorders of the nervous system, which affects an estimated 1 in 3,500 people.

The severity of NF1 can vary widely, even among family members, from mild dermatological symptoms to benign tumors that wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form, Dr. Le said. In addition, individuals with an improperly-functioning NF1 gene have an increased risk of developing cancerous tumors such as MPNSTs, he said.

The researchers generated a mouse model that spontaneously develops MPNSTs and compared gene expression activity in cancerous tumors and in the precursor cells that give rise to the tumors, which are the kind of cells in which MPNSTs develop.

They found that a protein (CXCR4), which is essential for tumor growth, is more abundant in cancerous cells than in precursor cells. In addition, they found that a molecule produced by the cancer cells themselves (CXCL12) works with CXCR4 to further the growth of cancer by stimulating the expression of the cyclin D1 protein, which promotes cell division via a signaling pathway outlined in the study.

When they examined human MPNSTs, the scientists found increased expression of CXCR4 accompanied by activity in the same pathway as the one identified in the mice, the researchers said.

Next, they blocked the activity of CXCR4 in the MPNST mice using either genetic manipulation or an FDA-approved antagonist drug for CXCR4 called AMD3100. Both strategies inhibited cancer development in mice whose tumors expressed increased levels of CXCR4, and were less effective in tumors without increased CXCR4 expression. They identified the same situation in the human cancer cells, the researchers report.

"We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today," said Dr. Le, who added that the researchers are currently planning human trials.


Contact: Deborah Wormser
UT Southwestern Medical Center

Related biology news :

1. Mesquite trees displacing Southwestern grasslands
2. Sea lamprey genome mapped with help from scientists at OU
3. Sequestration will be a devastating blow to the nations research institutions and scientists
4. Scientists explore topical health issues at meeting in Texas
5. Stanford scientists help shed light on key component of Chinas pollution problem
6. Fat worms inch scientists toward better biofuel production
7. Scientists create new maps depicting potential worldwide coral bleaching by 2056
8. Scientists find surprising new influence on cancer genes
9. Scientists find bone-marrow environment that helps produce infection-fighting T and B cells
10. MBL scientists find genes linked to human neurological disorders in sea lamprey genome
11. Scientists identify molecular system that could help develop treatments for Alzheimers disease
Post Your Comments:
Related Image:
UT Southwestern scientists make mouse model of human cancer, demonstrate cure
(Date:6/9/2016)... Paris Police Prefecture and ... ensure the safety of people and operations in several locations ... Teleste, an international technology group specialised in broadband ... its video security solution will be utilised by ... across the country. The system roll-out is scheduled for the ...
(Date:6/3/2016)... , June 3, 2016 ... von Nepal hat ... Lieferung hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, Registrierung ... in der Produktion und Implementierung von Identitätsmanagementlösungen. ... Ausschreibung im Januar teilgenommen, aber Decatur wurde ...
(Date:6/2/2016)... The Weather Company , an IBM Business (NYSE: IBM ... which consumers will be able to interact with IBM Watson ... or text and receive relevant information about the product or ... long sought an advertising solution that can create a one-to-one ... valuable; and can scale across millions of interactions and touchpoints. ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Mosio, ... second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with experienced clinical ... eBook by providing practical tips, tools, and strategies for clinical researchers. , “The ...
(Date:6/23/2016)... -- A person commits a crime, and the detective uses ... criminal down. An outbreak of foodborne illness makes ... uses DNA evidence to track down the bacteria that caused ... not. The FDA has increasingly used a complex, cutting-edge technology ... Put as simply as possible, whole genome sequencing is a ...
(Date:6/23/2016)...  The Biodesign Challenge (BDC), a university competition that ... living systems and biotechnology, announced its winning teams at ... New York City . The teams, ... at MoMA,s Celeste Bartos Theater during the daylong summit. ... curator of architecture and design, and Suzanne Lee ...
(Date:6/23/2016)... Durham, NC (PRWEB) , ... June 23, 2016 , ... ... Odense University Hospital in Denmark detail how a patient who developed lymphedema after being ... (fat) tissue. The results could change the paradigm for dealing with this debilitating, frequent ...
Breaking Biology Technology: