Telomerase and Cancer

 

 




Last night, I wrote,
    "For some reason, the fact that cancer cells express telomerase led some early researchers to suggest that perhaps telomerase would cause cancer if introduced into differentiated cells. Why that might be I'm not sure. Since cancer cells produce telomerase in profusion, it would seem to me as though cancer cells would be unaffected by telomerase, since they're already steeped in it. However, biological interactions are wickedly complex. I don't yet know enough to be dangerous."

    I've learned a little more about why some researchers are concerned about feeding someone telomerase.
    The problem is that some cells irreversibly stop dividing either because of shortening of their telomeres or because of some other genetic damage. This is thought to be a way of inhibiting damaged cells from reproducing, with a resulting higher risk of malignant transformation. If we gave someone a jolt of telomerase, it might permit these damaged cells to resume dividing, with disastrous consequences to the individual. Cell senescence may be one of nature's ways of reducing the likelihood of cancer.
    Dr. Judith Campisi has observed that the life expectancy for prehistoric humanity was, perhaps, 30 years. Most people failed to make it past 30, so the inability to generate telomerase would have been no problem for them, and would have helped to protect them from developing cancer. However, beyond age 30, the inability to express telomerase becomes a liability instead of an asset.
    "'We don't want to stop cellular aging,' asserted Judith Campisi, senior staff scientist at the Lawrence Berkeley National Laboratories, whose research focuses on the connections between aging and cancer.  'That would be a disaster.'  According, to Campisi, aging of cells is really a way of postponing cancer by allowing damaged cells to die and preventing cells from dividing.  Conversely, the way cancer is formed in older persons is through the changing functions of the cells that no longer divide; as the function of the cell changes, the possibility of mutation increases.
     "In addition to these findings and in spite of the general acceptance of the shortening of telomeres involvement in the aging process, there has been some evidence to the contrary.  Telomere shortening in yeast has led to cell death, not the phenotype seen in mammalian cell senescence, and although mice cells senesce faster than human cells in culture, mice telomeres are actually up to ten times as long as human telomeres and do not shorten over the lifetime.           
    I have a few questions with respect to this model. Some human cells do express telomerase:  those that must continually divide, such as the hematopoietic cells in bone marrow that produce red blood cells, and the keratocytes in the skin that produce new epidermal cells (and. I suspect, the hair follicles). The cancer rates in these tissues are no higher than they are in other tissues. Skin cancer is relatively benign except for melanomas, and I've never heard of cancer in hair follicles. That suggests (to me) that the presence of telomerase doesn't have to be harmful. One recent paper (August 30, 2002) shows that in these highly proliferative human cells that express telomerase, the telomerase is walled off in the nucleolus until just before cell division, when it suddenly appears throughout the nucleus. By contrast, in cancer cells  telomerase is everywhere in the nucleus throughout the entire cell cycle. However, when both a normal cell and a malignant cell were irradiated to cause chromosome breaks, the telomerase was swept up in the nuclei of both types of cells and sequestered in their nucleoli, presumably to keep the broken chromosome ends from acquiring telomeres before they could be repaired.
    See also Be fruitful and immortalize.
    One interesting article (LE Magazine, June 2002 - Cracking the Secrets of Aging) describes work on a telomerase pill that might maintain human telomere lengths if taken every two years.