Navigation Links
Extracellular protein sensitizes ovarian cancer cells to chemotherapy
Date:12/10/2007

Scientists have uncovered critical new details about the mechanisms that modulate the response of ovarian cancer cells to chemotherapy. The research, published by Cell Press in the December issue of Cancer Cell, helps to explain why many patients develop resistance to the taxane class of drugs and may lead to improved treatment of ovarian cancer.

Cancer cells divide rapidly and undergo extensive microtubule-driven restructuring as they proliferate. Taxanes, such as paclitaxel (Taxol), interfere with the dynamic growth of microtubules by directly binding to them and making them more stable and, as a result, disrupt the normal process of cell division. Paclitaxel has been used extensively to treat lung, ovarian and breast cancers but drug resistance limits the clinical usefulness of this drug to only about half of breast or ovarian cancer patients.

Although it is clear that taxane resistance is associated with a loss of stable microtubules and that microtubule stability can be influenced by signals from the extracellular matrix (ECM), a role for ECM proteins in the modulation of paclitaxel sensitivity has not been established. To explore the connection between regulation of microtubules and taxane resistance, Dr. James D. Brenton from the Cancer Research UK Cambridge Research Institute in Cambridge, England and colleagues performed an extensive examination of ovarian cancer cell lines that were sensitive or resistant to paclitaxel.

The researchers found that the ECM protein, transforming growth factor beta induced (TGFBI), was significantly reduced in paclitaxel-resistant cells. Importantly, TGFBI mediated sensitization to paclitaxel and loss of TGFBI was sufficient to induce paclitaxel resistance. TGFBI induced microtubule stabilization that was dependent on integrin-mediated FAK and Rho signaling. Further, analysis of ovarian cancer samples taken after treatment with paclitaxel revealed that paclitaxel-induced cell death was associated with high levels of TGFBI expression.

These results identify TGFBI as an ECM protein that induces microtubule stability and modulates sensitivity to paclitaxel in ovarian cell lines and in patients receiving paclitaxel therapy. Our findings have potentially significant clinical applications as TGFBI protein expression is lost in one third of primary ovarian and lung cancers and FAK is low or absent in one-third of ovarian cancer patients, explains Dr. Brenton. It is possible that TGFBI could be used as a biomarker for selecting patients likely to respond to taxane therapy. In addition, proteins that activate TGFBI or mimic its action may be an effective strategy for modulating the response to widely used drugs like paclitaxel or docetaxel.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Draining away brains toxic protein to stop Alzheimers
2. Penn study finds pro-death proteins required to regulate healthy immune function
3. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
4. Emory researchers identify signaling protein for multiple myeloma
5. Human C-reactive protein regulates myeloma tumor cell growth and survival
6. Lowering Blood Protein Wont Help Kidney Patients
7. Blood protein detects lung cancer, even at earliest stage
8. Natural Protein Could Help Spot, Treat Liver Cancer
9. Heat shock proteins are co-opted for cancer
10. How adhesive protein causes malaria
11. Loss of gene leads to protein splicing and buildup of toxic proteins in neurons
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... ... April 29, 2016 , ... ... Foundation, the national charitable foundation serving the footwear industry, has broken all previous ... more than 130 companies across 23 states during the months of April and ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... Awakening , announces the addition Onnit brand Alpha BRAIN and New Mood Daily-Stress ... Onnit brain and mood optimization products to the store is just one more ...
(Date:4/29/2016)... ... April 29, 2016 , ... On Tuesday, April 26, ... the Southeast, celebrated the signature of Gov. Nathan Deal on SB 258, the “Rural ... (R - Cumming), offers a 70% tax credit to individuals and corporations which donate ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... and author of best seller "LOVE, MEDICINE and MIRACLES") addresses touchy topics related ... 2016 and podcasted thereafter . Dr. Bernie Siegel, author of a plethora ...
(Date:4/29/2016)... STAMFORD, CONNECTICUT (PRWEB) , ... April 29, 2016 , ... ... 5K Run/Walk” at Cove Island Park on Sunday, with sunny skies, a light breeze ... event, raising nearly $33,000. , The 5k Run and Walk and 1-mile ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... Oramed Pharmaceuticals Inc. (NASDAQ: ... on the development of oral drug delivery systems, announced today ... conference, presented by Joseph Gunnar & Co. LLC, ... York . Nadav Kidron , CEO of Oramed, ... Presentation Details:   PIONEERS 2016, presented by ...
(Date:4/28/2016)... New market research titled ... report that provides an overview of the Osteoarthritis,s ... identifying new targets and MOAs to produce first-in-class ... in this H1 2016 Osteoarthritis Pipeline report include ... Abiogen Pharma S.p.A., Ablynx NV, Achelios Therapeutics, Inc., ...
(Date:4/27/2016)... April 27, 2016   ... Growth in Recurring Consumable Sales  Clinical sales ... Kea Technologies (Euronext: MKEA, OTCQX: MKEAY) inventor of Cellvizio®, ... sales for the first quarter ended March 31, 2016 ... execution of its commercial strategy. First Quarter ...
Breaking Medicine Technology: