Navigation Links
Cancer cell behavior during Metastasis – New finding

A recent study in rats proposes that the highly malignant tumor cells possess a "toggle switch" that allows them to convert into highly mobile cells// , which attack other tissues and nest in their new environment.

According to the Duke Comprehensive Cancer Center researchers, this finding of the two alternating forms of tumor cells; travelers and nesters reveals how cancer mestasizes i.e., spreads to other body parts.

"Understanding this toggle switch might ultimately enable scientists to find ways to stop cells from metastasizing, which is the most deadly trait of cancer," said the study's lead investigator, Mariano Garcia-Blanco, M.D., Ph.D., professor of molecular genetics and microbiology.

The researchers will publish their findings in the Sept. 19, 2006, issue of the journal Proceedings of the National Academy of Sciences, now available on line. The research was funded by the National Cancer Institute.

Until now, scientists have believed that cancer cells must transform permanently from stationary epithelial cells into migratory mesenchymal cells in order to metastasize. The Duke team discovered that highly malignant cells are equal parts epithelial and mesenchymal, transitioning between the two as their surroundings necessitate. The proteins that the cell produces dictate which way the cell shifts.

In a classic example of survival of the fittest, a cancer cell's ability to toggle between epithelial and mesenchymal enables the most malignant cells to aggressively invade and then peacefully adapt in unfamiliar territory, the scientists said.

"The prevailing notion has been that the more mesenchymal the cancer cells, the more mobile and metastatic they would be," Garcia-Blanco said. "In reality, aggressive cancer cells are not homogenous, but are extremely versatile in their ability to adapt as their survival needs shift." The researchers discovered this transition in cancer cells when they observe d an error in "alternative splicing," a key element of the genetic copying program inside cells. Alternative splicing determines how the DNA is chopped into pieces and then reassembled. The order in which DNA is reassembled determines which proteins the gene produces.

In cancer cells, the splicing machinery goes awry -- as do myriad functions within the cells. When the splicing process proceeds one way, the cells become mesenchymal. Spliced another way, the cells turn epithelial.

To determine which way a cancer cell would turn, the scientists constructed a fluorescent "reporter" -- a protein that illuminates if the cell turns epithelial but lies dormant if the cell reverts to mesenchymal state. By following the reporter's illumination within cancer cells in rats, the team viewed the very process of alternative splicing as it occurred in the tumors. The researchers were able to visualize specific portions of DNA, called exons, to see if they were included or excluded in the splicing process as the cell transformed.

"We found that the regulation of alternative splicing is different in mesenchymal versus epithelial cells," Garcia-Blanco said. "A particular exon, FGFR2 IIIc, is silenced in mesenchymal cells but is active in epithelial cells. "We can visualize the genes as they are dynamically changing," he said. "We can define the cell types by observing their splicing patterns."

According to Garcia-Blanco, the cellular switch that is believed to guide the regulation of splicing is a protein called Fox. Both mesenchymal and epithelial cells produce Fox, but the protein is active only in epithelial cells, Garcia-Blanco said.

Fox also may have an accomplice or "co-factor" in or around epithelial cells that prompts it to activate, the researchers said. They speculate that this co-factor could be activated by contact with stroma --the supporting structural cells of a tumor -- because the stroma is where the majority of epi thelial-type cancer cells were observed. Their heavy presence implies that the stroma may have induced the cancer cells to revert to epithelial when they reached a new destination, so they could stabilize to populate a new tumor site.

"Our findings validate that tumors are highly complex in their behavior and don't necessarily need a gene mutation to alter their behavior," said Sebastian Oltean, M.D., Ph.D., research associate and first author of the journal article. "Alterations in gene splicing can be much more subtle in nature but still have a major impact on the cancer cell and can be targets of therapy."

The team's next step is to determine precisely what controls the toggle mechanism in cancer cells, Garcia-Blanco said. Identifying the various steps that occur during the natural progression of tumors could lead to therapies for blocking metastasis, he said.

Source-Eurekalert
GYT
'"/>




Related medicine news :

1. Fibroids unlikely to Turn Cancerous
2. Virus Level could Predict Cervical Cancer Risk
3. Cancer Doctors Okays Controversial Prostate Therapy
4. Potential New Cancer Gene Identified
5. Consensus on "Combination Therapy" for Breast Cancer
6. Cancers of Colon & Rectum linked to Cigarette Smoking
7. Life Saving Cancer Drugs – From Chicken! Possible Says Dolly’ Creatos
8. The Cancer Rumour mill working over time
9. Cancer drugs in development nearly doubled since 1995
10. Radioactive Seeds used in Prostate Cancer treatment can migrate with the body
11. Cancer patients turning to Internet for information
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/24/2016)... ... May 24, 2016 , ... Clarion ... and safety labels , has been featured in the National Electrical Manufacturers ... eiXtra e-newsletter provides electroindustry professionals with manufacturer, regulatory, and standardization news. The publication ...
(Date:5/24/2016)... ... , ... Since 1946, the doctors and staff at Clifton Dental Associates have ... arrives at the office, the staff will make them feel welcome and comfortable. Drs. ... a complete dental treatment plan that is unique to each smile. , Dr. Kayne ...
(Date:5/24/2016)... ... May 24, 2016 , ... PhysicianOne Urgent Care, advocators in ... tick bites and how to avoid being bitten this spring. , The official ... , Ticks, small spider-like insects, are known for attaching themselves to their prey while ...
(Date:5/24/2016)... ... May 24, 2016 , ... Today ... module. The cutting-edge feature provides end users with an embedded, real time ... intelligence solution and its analytics engine. , This powerful addition to ...
(Date:5/24/2016)... TN (PRWEB) , ... May 24, 2016 , ... ... vitamin alkaline water, a revolutionary new beverage for pregnant women to prevent morning ... prenatal vitamins and alkaline minerals with the look and taste of water. , ...
Breaking Medicine News(10 mins):
(Date:5/19/2016)... COUNTY, Calif. , May 19, 2016 /PRNewswire/ ... two thirds of the world lacks basic diagnostic ... procedures in the United States ... privileged to such technology. In fact, the WHO ... at risk of avoidable or treatable death, simply ...
(Date:5/19/2016)... -- According to a new market research report "Sunitinib ... Germany , France , U.K., ... Japan )", published by MarketsandMarkets, The market is projected ... 13.9% from 2016 to 2021.      (Logo: http://photos.prnewswire.com/prnh/20160303/792302 ... spread through 26 Pages and in-depth TOC on "Sunitinib ...
(Date:5/19/2016)... , The data will be presented in ... The conclusions of the study point to a ... 90% of the m presenting duration ... of the patients had clinical benefit.     ... study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed ...
Breaking Medicine Technology: