Navigation Links
Tumor cells that border normal tissue are told to leave

The thin, single-cell boundary where a tumor meets normal tissue is the most dangerous part of a cancer according to a new study by scientists at Washington University School of Medicine in St. Louis. The researchers found that tumor cells bordering normal tissue receive signals that tell them to wander away from the tumor, allowing the cancer cells to establish deadly metastatic tumors elsewhere in the body.

The researchers say their discovery demonstrates the importance of the tumor's environment and shows more precisely how the metastatic process occurs and might be stopped. Their study appears in the January 10 issue of Developmental Cell.

"What actually kills in cancer is not the primary tumor--it's metastasis," says senior author Ross L. Cagan, Ph.D., associate professor of molecular biology and pharmacology and a researcher with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "You can't study that in a laboratory dish. You have to look at the tumor cells in their natural environment--surrounded by normal tissues."

To do this, the research team created tumors in fruit fly eyes and wings that permitted them to study the behavior of individual tumor cells.

"We found that the tumor cells in direct contact with normal cells had a different behavior than cells further inside the tumor," says lead author Marcos Vidal, Ph.D., research associate in molecular biology and pharmacology. "They were exclusively the ones that tended to leave the tissue."

The tumors were generated by turning off an inhibitor of a major oncogene called Src (pronounced sarc), making the tumor cells high in Src oncogene activity. (An oncogene is a gene that increases the malignancy of a tumor cell.) This particular genetic change is common in human breast tumors.

Boundary tumor cells were shown to lose surface proteins that attach them to other cells and stabilize their position within tissues. T he study demonstrated that it was the difference in Src activity that led to the change in the attachment proteins. When a high Src cell (tumor cell) was next to a low Src cell (normal cell) the attachment proteins changed their characteristics, and the high Src cell became "unglued."

In addition, this change sent a signal that activated several other proteins in the tumor cell, one of which was an enzyme that dissolves the matrix surrounding cells. This enzyme makes it possible for a cell to move through tissues.

"Even though all the cells in the tumors we created were genetically identical, the proximity of the boundary cells to normal cells--their interaction with normal cells--made them special," Vidal says. "This is the first time the epithelial environment has been shown to play a role in metastasis."

The cells that left the fruit fly tumors eventually succumbed to the natural process of programmed cell death and were eliminated. According to Cagan, that was not unexpected.

"In a tumor, probably 99.99 percent of the border cells are raining out of the edges and dying," Cagan says. "But as oncologists have found, cancer stems from an accumulation of genetic mutations. If one of these wandering cells acquires a second mutation that prevents cell death, it could go on to establish a metastatic tumor."

Having created a model for studying metastasis of tumor cells, the research team has begun to look for ways to manipulate boundary cells to prevent their metastatic behavior. They have seen that disabling some of the genes in the pathway activated in boundary cells stops the cells from leaving the tumor.

Cagan's laboratory also has developed a robotic system for screening anticancer drugs, and they plan to use this system to look for drugs that will affect the metastatic process in their fruit fly model.

"A drug that can prevent metastasis would be an important adjunct for cancer treatments," Cagan says. "It co uld cut a patient's risk of having tumor cells leave the area before the primary tumor was eradicated. That's essential--metastatic cancer is far harder to treat than early-stage tumors."


'"/>

Source:Washington University School of Medicine


Related biology news :

1. Missing Receptor Molecule Causes Tumor Growth
2. Stem Cells Found In Cerebellum; Possible Cell of Origin for Childhood Brain Tumors
3. New Therapeutic Target Identified In Inherited Brain Tumor Disorder
4. Tumor wizardry wards off attacks from the immune system
5. Tumor cells evade death through autophagy
6. Tumor-suppressor gene is critical for placenta development
7. Wisconsin scientists grow critical nerve cells
8. Spleen may be source of versatile stem cells
9. Researchers discover way to make cells in the eye sensitive to light
10. Priming embryonic stem cells to fulfill their promise
11. Lack of enzyme turns fat cells into fat burners
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/23/2017)... ITHACA, N.Y. , June 23, 2017  IBM ... in dairy research, today announced a new collaboration using ... the chances that the global milk supply is impacted ... project, Cornell University has become the newest academic institution ... Chain, a food safety initiative that includes IBM Research, ...
(Date:5/16/2017)... , May 16, 2017  Veratad Technologies, LLC ( ... online age and identity verification solutions, announced today they ... Conference 2017, May 15 thru May 17, 2017, in ... and International Trade Center. Identity impacts ... and in today,s quickly evolving digital world, defining identity ...
(Date:4/24/2017)... , April 24, 2017 ... and partner with  Identity Strategy Partners, LLP (IdSP) ... "With or without President Trump,s March 6, 2017 ... Terrorist Entry , refugee vetting can be instilled with ... resettlement. (Right now, all refugee applications are suspended ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... Alto, CA, USA (PRWEB) , ... October 11, 2017 , ... ... set to take place on 7th and 8th June 2018 in San Francisco, CA. ... policy influencers as well as several distinguished CEOs, board directors and government officials from ...
(Date:10/11/2017)... TX (PRWEB) , ... October 11, 2017 , ... ... August compared the implantation and pregnancy rates in frozen and fresh in ... contribution of progesterone and maternal age to IVF success. , After comparing the ...
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... Dr. Bob ... at his local San Diego Rotary Club. The event entitled “Stem ... CA and had 300+ attendees. Dr. Harman, DVM, MPVM was joined by two ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: