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:12/6/2016)... ... December 06, 2016 , ... Gateway ... now offering HIAC particle counting and sizing services for USP 788 and 789 ... the new service as a response to the needs of pharmaceutical and medical ...
(Date:12/6/2016)... (PRWEB) , ... December 06, 2016 , ... 'Tis the ... disrupt daily routines. That means it's also the season when eating healthy, staying active, ... with diabetes) on schedule is harder to do. , "Shopping trips, parties and ...
(Date:12/6/2016)... ... December 06, 2016 , ... ... the only authorized OSHA Training Institute Education Center headquartered in Northern California, has ... focused on providing occupational safety and health training to public sector employees. , ...
(Date:12/5/2016)... ... December 05, 2016 , ... ... Surgery, is excited to announce the arrival of the newest Sciton laser in ... the ability to use tunable non-ablative and ablative wavelengths for exceptional results. Outperforming ...
(Date:12/5/2016)... ... 05, 2016 , ... Researchers at Johns Hopkins All Children’s Hospital want to ... Over the course of three years, researchers will study concussions and changes in brain ... equipped with special sensors, will track the location and force of the hit. The ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... Dec. 5 2016 United Kingdom Ophthalmic ... GlobalData,s new report, "United Kingdom Ophthalmic Diagnostic ... data on the United Kingdom Ophthalmic Diagnostic Equipment ... US dollars, volume (in units) and average prices ... (OCT), Retinal Ultrasound Imaging Systems, Corneal Topography Systems, ...
(Date:12/5/2016)... Dec. 5, 2016   Mallinckrodt Pharmaceuticals (NYSE: ... company, today announced that it received a perfect score ... (CEI), a national benchmarking survey and report on corporate ... transgender (LGBT) workplace equality, administered by the Human Rights ... major U.S. businesses which also earned top marks this ...
(Date:12/5/2016)... Dec. 5, 2016  Cornerstone Pharmaceuticals, Inc., a ... data from two Phase I trials evaluating its ... 58th annual meeting of the American Society of ... . The two datasets show encouraging efficacy ... leukemia (AML) and T-cell non-Hodgkin,s lymphoma (T-cell NHL), ...
Breaking Medicine Technology: