Navigation Links
Loss of cell adhesion protein drives esophageal and oral cancers in mice
Date:4/12/2011

PHILADELPHIA - Squamous cell cancers of the oral cavity and esophagus are common throughout the world, with over 650,000 cases of oral cancer each year and esophageal cancer representing the sixth most common cause of cancer death in men. Research by University of Pennsylvania School of Medicine investigators has shown that a protein that helps cells stick together is frequently absent or out of place in these cancers, but it's unclear if its loss causes the tumors.

The investigators report that mice engineered to lack this protein, called p120-catenin (p120ctn), in the oral-upper digestive tract develop squamous cell cancers. The data, reported Cancer Cell, settle a 20-year debate and prove that p120ctn is a tumor-suppressor protein. What's more, the tumors that form in this mouse model closely resemble human disease and may point the way to novel therapies and early detection strategies.

"As the mice aged, what we saw was a dramatic evolution of precancer to cancer," says senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and Genetics and chief of Gastroenterology. "Both the precancerous growth, called dysplasia, and the cancer look exactly like what we see in humans. This is really exciting because it supports efforts for prevention and early detection, especially in people who drink alcohol and smoke cigarettes excessively and are at high risk for the disease in many regions of the world."

In healthy tissues, p120ctn is part of a protein complex that holds epithelial cells in tightly packed sheets. When p120ctn (or another of these cell adhesion proteins) is lost, a wide variety of cancers including those in prostate, breast, pancreas, colon, skin, bladder, and the endometrium, can result.

The cells lose their tight cell-cell contacts and can migrate more easily, which likely favors cancer spread and invasion of new cells. However, earlier attempts to test the effects of p120ctn loss on cancer formation were derailed because the animals cannot survive throughout embryonic development or immediately after birth without the protein.

To get around that problem, Rustgi and colleagues used a system called Cre-Lox that allows them to remove a particular gene in only a subset of tissues. In this case, the team deleted p120ctn from the oral cavity, esophagus and forestomach. The mutant animals survived through early development and birth, but by 4 to 6 months, most of the mutant animals had developed precancerous lesions and by 9 to 12 months, 70 percent of the mutant animals had full blown tumors. By contrast, none of the control littermates developed cancer.

The investigators noted that as the lesions developed, the tumor cells secreted inflammatory signals that acted like homing signals for immune cells called immature myeloid cells. These cells, in turn, helped to create a microenvironment that supported tumor growth. In fact, when the researchers blocked recruitment of the immune cells, they saw a dramatic reduction in tumor invasion.

Based on these observations, Rustgi thinks that targeting the immature myeloid cells may reverse or slow tumor grown in humans, although more work needs to be done in animal models before the approach is tested in the clinic.

Rustgi says that the mouse model will help test innovative therapies and early detection tests. He says that although he was born and raised in the United States, he was influenced by five years he spent as a child in India, where oral cancer is common due to the proportion of the population that chews betel nuts. "I remember, even as a little kid, I would see people with oral lesions," he says. "I didn't know what they were then, but it has always motivated me at a personal level. Esophageal cancer biology has also been a long-standing interest of mine because it affects so many underserved people in the inner cities in the United States."


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. New and Delicious, Almond Butter Filled, Cookie Bites With 35.7% Protein to Help Manage Weight and Build Muscle
2. Research highlights role of protein pair in obesity regulation
3. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
4. Smithfield, United Food and Commercial Workers Union, and Food Networks Paula Deen to Deliver 150,000 Servings of Protein to San Francisco Food Bank
5. Protein Sciences Corporation Announces Profitable and Cash Flow Positive Results for 2009 and Management Realignment
6. Protein Appears Key to Intestinal Balance
7. SIBLING proteins may predict oral cancer
8. Damaged protein identified as early diagnostic biomarker for Alzheimers disease in healthy adults
9. Cells of aggressive leukemia hijack normal protein to grow
10. Omega Protein Comments on California Lawsuit Alleging Fish Oil Contaminants
11. Proteins May Predict Spread of Colon Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/29/2017)... ... March 29, 2017 , ... Wells Pharmacy Network, ... prescribers at the upcoming World Congress, in Hollywood Florida April 6-8, 2017. , ... as the visionary leader in the training of physicians, scientists, and members of ...
(Date:3/29/2017)... ... 29, 2017 , ... The Wall Centre Dental team is ... from Burnaby, BC. Patients in need of experienced orthodontics, laser dentistry, porcelain veneers, ... esteemed team at Wall Centre Dental. Drs. Parviz Roshan, Siamak Tehrani, Milton Reskovich ...
(Date:3/29/2017)... ... 2017 , ... Patients interested in receiving quick and effective ... Cameron, with or without a referral. The FASTBRACES system is valued for its ... patient’s case, treatment with the FASTBRACES system could be completed in 120 days ...
(Date:3/29/2017)... Mich. (PRWEB) , ... March ... ... and Manufacturer Alliance (GRMA) is growing as it continues developing an ANSI-approved, ... supplement industry. The organization, which plans to publish the first ANSI-approved GMP ...
(Date:3/29/2017)... ... March 29, 2017 , ... Altima Technologies, ... diagramming network and data center assets and audio-video devices has recently updated its ... equipment shapes for free and download shapes and stencils from http://www.VisioStencils.com. ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... 29, 2017  Maxor National Pharmacy Services, LLC ("Maxor"), ... has named Leah Bailey as General Counsel.  Bailey ... the company. With more than 13 years ... years focused on health care, Bailey joins the Maxor ... Prime, Bailey advised the PBM, Specialty, and Mail Order ...
(Date:3/29/2017)... 2017 Varian Medical Systems (NYSE: VAR ... second quarter of fiscal year 2017 following the close of ... will be followed by a teleconference available to all interested ... link to the conference call webcast will be available on ... teleconference call and replay: ...
(Date:3/29/2017)...  Spiral Therapeutics, Inc. today announced the signature ... for the worldwide exclusive rights to Bionure,s lead ... of otolaryngology for aggregate payments of up to ... provides Spiral with the option to license two ... Under the terms of the agreement, Spiral will ...
Breaking Medicine Technology: