A graphic demonstration of the importance of the extracellular matrix (ECM) to cell functions was accomplished using two unique lines of human mammary epithelial cells, one that remains normal (a) and one that becomes malignant (b) following a known sequence of events.
The malignant breast cell strain was treated in culture with an antibody that blocks one of the kind of proteins called integrins, which reside in the outer membrane of a cell and through which signals from the ECM are transmitted inside.
Under the influence of the integrin-blocking antibody, the malignant cells reverted back to a normal appearance (c); their cancerous growth ceased, and they looked and functioned as if they were normal breast cells. When the reverted cells were examined with a fluorescent probe, the genes in their nuclei were still abnormal, indicating that the phenotype had been changed but not the genotype.
Altering the microenvironments of genetically nonmalignant human breast cells with other integrin-blocking antibodies caused those cells to look and act malignant.
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The importance of ICE Controlled death is as much a part of normal cell development and functioning as controlled growth and differentiation. If a cell does not die when it is supposed to, problems occur throughout the rest of the cycle that can lead to the development and spread of cancer. Berkeley Lab's Mina Bissell and long-time collaborator Zena Werb, a professor at the University of California at San Francisco, have shown that a breakdown of the extracellular matrix results in an abnormally high rate of apoptosis -- programmed cell death -- another significant factor in the development of breast cancer. The process revolves around the expression of a protein called the interleukin-1-beta converting enzyme (ICE). Apoptosis is induced by activation of ICE, which correlates with the loss of ECM. When ECM is present, however, the activity of ICE is inhibited, and apoptosis occurs at the proper time and rate. In normal breast cells, ICE becomes active at the end of lactation, when milk production is no longer necessary and the breast must remodel itself. |
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