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Interactions, Relationships, Rogues and Enablers Wield Influence in Macro and Micro Environments

Posted By Prucia Buscell, Thursday, December 31, 2009
Updated: Thursday, February 17, 2011
Biological cells may react to their environments somewhat akin to the way children are influenced by their neighborhoods and schools, an increasing number of scientists believe. Cell biologist Mina Bissell believes a key element in the formation of cancer is not just what happens within a cell, but the interactions of cells and all the tissue surrounding them. With certain environmental changes, cancer cells that might have remained harmless can flourish.

Dr. Bissell, Distinguished Scientist at the Lawrence Berkeley National Laboratory, has been researching the behavior of cancerous cells and gene mutations for three decades."Old Ideas Spur New Approaches in Cancer Fight", a December 29 New York Times story by Gina Kolata, describes how the work of Dr. Bissell and others is beginning to change the way scientists think about cancer. Scholars, pharmaceutical companies, and even former scientific skeptics are beginning to realize that the micro-environment of cancerous cells can't be ignored.

"Thinking Outside the Cell," a story by Kara Platoni, quotes Dr. Nancy Boudreau, one of Dr. Bissell's post-doctoral fellows who now directs the surgical research laboratory at the University of California at San Francisco, on Dr. Bissell's innovative scientific approach: Dr. Bissell was investigating overall function at a time when most other researchers were looking at individual components. Dr. Boudreau recalls an experiment in Dr. Bissell's lab in which mammary cells essentially committed suicide after tissue around them was destroyed. As Dr. Boudreau explains it, cells fit into a communication network provided by the matrix, or surrounding material, and when both are communicating correctly, the potential for malignancy is kept in check. When signaling between cell and matrix is disrupted by age, inflammation or other adversities in the micro-environment, the cell loses its social context. In the resulting disorder, she says, "the tumor cell is like a nutjob on the street that says "I don't care'."

Zena Werb, vice chair of the anatomy department at UCSF,a friend and frequent collaborator with Dr. Bissell, observes children and cells absorb environmental influences: A smart youngster raised in an environment where crime pays may excel at criminality, and the same youngster raised in an environment that rewards scholarship might become a concert pianist. So will a rogue cell behave normally if its environment is changed? Possibly.

In a 1997 paper in the Journal of Cell Biology, Dr. Bissell reported that breast tumor cells dosed with a certain antibody reverted to a normal state. In a 1999 paper she reported that previously normal mouse mammary cells underwent malignant or premalignant gene changes when their micro-environment was degraded, disrupting communication between the cells and their matrix.

Others who have pursued similar ideasare also receiving belated recognition. The Times story notes Dr. D. W. Smithers wrote in a 1962 article in The Lancet that cancer is a disorder of cellular organization, and not one of malignant cells that run amok and kill the host. The Times story also says in 1975, another cancer scientist, Beatrice Mintz, of the Fox Chase Cancer Center in Philadelphia, inserted mouse cancer cells into mouse embryos. The embryos developed normally, even though the remained present as the mouse grew. But injection with the same cells would kill an adult mouse. Dr. Bissell was fascinated by the work. She and one of her students found that a virus that caused fatal tumors when injected into adult chickens did not cause cancer in chickens whose embryos had been injected with the cells.

Dr. Bisselll's work also provides clues on why some cancers develop after wounds and injuries, and why the US breast cancer rate in women over age 50 dropped 15 percent in 2003 and the next year. Hormone therapy for menopausal women declined after a 2002 federal study that the treatment actually produced a slight risk for heart disease and breast cancer, the story says, and scientists now suspect the therapy may have changed the structure and activity of breast tissuein ways associated with higher cancer risk.

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