Nav: Home

New strategy may drop cancer's guard

November 30, 2016

HOUSTON - (Nov. 30, 2016) - A drug used now to treat Type 2 diabetes may someday help beat breast and ovarian cancers, but not until researchers decode the complex interactions that in some cases help promote tumors, according to Rice University scientists.

Rice bioscientist Daniel Carson and alumna Micaela Morgado researched thiazolidinediones, small molecules used to fight diabetes, that can halt the expression of glycoproteins that make up the protective mucus that lines cells and organs in the body. These mucus cells are manipulated by tumors to keep them safe from chemotherapy and the immune system.

But there are problems to be solved before the drug can be used to fight cancer, Carson said, including the fact that small doses appropriate for diabetes treatment actually increase cancer risk for patients with diabetes. The drug they studied, rosiglitazone, shows promise only if it can be delivered in large-enough doses and directly to tumors, he said.

The work will appear in the January issue of the Journal of Cellular Biochemistry.

"My lab is interested in the class of very high-molecular-weight glycoproteins that absorb water and cover and protect the surfaces of your cells," Carson said. "These mucins perform a very important protective function, lining your mouth, your glandular structures and your gastrointestinal tract, essentially acting like Teflon for those surfaces.

"But tumors have learned a trick," he said. "Instead of keeping mucins on one end of a cell, where they would normally protect it from the external environment, they start putting mucins all over their surfaces. Cells of the immune system that kill tumors have to make contact with the cancer cell's surface, but when they have these big barrier molecules on the surface, they're protected.

"If we can intervene in patients and reduce mucin levels, maybe the host immune system can do its job and kill the tumors," Carson said.

The lab studied the effects of one thiazolidinedione, rosiglitazone, on a glycoprotein known as MUC16 that protects breast and ovarian cancer cells. Another, pioglitazone, was the focus of a recent Rice breast cancer study, and Carson's lab previously studied the effects of rosiglitazone on another glycoprotein, MUC1.

"MUC16 wound up being particularly interesting because it's also known as CA125, which is the gold standard marker for ovarian cancer," he said. "Women are routinely monitored for CA125 levels that normally are found at very low levels in serum. If you have certain tumors, these cancer cells begin to release fragments of CA125."

Carson said doses of rosiglitazone fed to cancer cell lines in the lab shut down the production of glycoproteins by interfering with the actions of cytokines that trigger the cells' protective response and elevate MUC16 production.

"It turns out the tumor microenvironment is rich in these cytokines," he said. "You would think these pro-inflammatory mediators would be a good thing because they enhance the immune response to the tumor. But, in fact, they also enhance the tumor's protective response."

He said stopping production of MUC16 for even a couple of days might be enough to breach the protective shield and allow immune cells to begin the destruction of a tumor. "If you could shut down synthesis by 90 percent or more, which is achievable with these drugs, within two days you have enough reduction to remove the tumor's protective coating.

"There's nothing here we can take to a clinic yet," Carson said. "We learned about ways to intervene and reduce the expression, but we either need better drugs that can do it at much lower, pharmacologically achievable levels, or we need to have a way to target drugs so we can get tumor-specific, superphysiological concentrations that would achieve the goal.

"The upside is that these drugs are already FDA approved," he said. "If we can repurpose them, we don't have to go through the same duration of regulatory process required to use them for cancer therapy."
-end-
Morgado is now a postdoctoral researcher at Yale University Medical School. Carson is the Schlumberger Chair of Advanced Studies and Research and a professor of biosciences at Rice.

The Rice University Fellowship Fund and Rice University Institute of Biosciences and Bioengineering Medical Innovation Fund supported the research.

Read the abstract at http://onlinelibrary.wiley.com/doi/10.1002/jcb.25622/full.

This news release can be found online at http://news.rice.edu/2016/11/30/new-strategy-may-drop-cancers-guard/

Follow Rice News and Media Relations via Twitter @RiceUNews

Related materials:

Daniel Carson bio: http://biosciences.rice.edu/facultydetail.aspx?riceid=184636

Wiess School of Natural Sciences: http://natsci.rice.edu

Image for download:

http://news.rice.edu/files/2016/11/1205_CANCER-1-web-1s2egu3.jpg

An image of endometrial cancer tissues shows cell nuclei (blue), an epithelial marker protein called E-cadherin (green) and MUC16 glycoproteins (red) that are suspected of protecting tumors. Rice University researchers discovered that a drug used now to treat Type 2 diabetes might help battle breast and ovarian cancers by manipulating the interactions that overexpress the protective mucus that tumors use to defend against chemotherapy and the body's immune system. (Credit: Carson Lab/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for happiest students and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/RiceUniversityoverview.

Rice University

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".