Dying Cells: A New Approach to Combating Cancer





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Mina Bissell of the Lawrence Berkeley National Laboratory may have taken a giant step closer to discovering a cure to one of the most common and incurable diseases-cancer.

Diseased and damaged cells are often subject to a process called programmed death, or "apoptosis."

Chemotherapy, a form of artificially-induced apoptosis, is a common treatment for cancer. In chemotherapy, doctors use specific chemicals that seek out and destroy malignant tumor cells.

The technique isn't 100 percent effective at making cancer manageable. Some tumor cells will often just refuse to die.

Bissell attributed a surprising new factor to cells' ability to resist apoptosis-their structure and resulting polarity, which means looking in three dimensions.

"We developed a 3-D model in which we put cells in an abbreviated cellular matrix, which is the material outside of cells," Bissell said. "We now have shown that many genes and pathways behave very differently in three dimensions than when they do in two."

The research conducted by Bissell and her team showed that malignant tumor cells that manage to mesh themselves within the body's natural cell structure-in a glandular cell-are more resistant to drug-induced apoptosis.

Some malignant tumor cells exhibit this apoptosis-resistant property without actually being arranged into glandular cells. These cells acquire the virtue of being coated with a specific cell-adhesion integrin which almost mimics being arranged into a glandular shape.

University of Pennsylvania professor Valerie Weaver was a co-author of the study, which was published in the September 2002 issue of the journal Cancer Cell.

Traditional medical doctrine states that many tumor cells erupt as a series of gene mutations in built-in tumor suppressors, Weaver said.

Bissell and Weaver's findings have nevertheless faced skepticism.

"The relevance of the 'newer integrative perspective' is quite powerful but considering the scientific community's current honeymoon with the genome project and the single molecule perspective our ideas are not always met with great enthusiasm," Weaver said. "So it has been rather difficult over the years to convince others of the importance of our work."

If cells are indeed more susceptible to drug-induced apoptosis based on their polarity, then new chemotherapy methods could be developed to more effectively target cancerous cells.

"I believe that to understand tumor behavior we must think about things from an integrated perspective and consider tissue organization and tissue microenvironment as key elements in tumor progression particularly with respect to generating better cancer therapies," Weaver added.

Both Weaver and Bissell intend to further investigate the importance of tissue organization as it relates to normal and abnormal cell behavior, but Weaver intends to simultaneously focus on apoptosis-resistance.

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