|
|
Back
Senescent
fibroblasts promote epithelial cell growth and tumorigenesis: A link
between cancer and aging.
Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J.
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley,
CA 94720; and Geraldine Brush Cancer Research Institute, California
Pacific Medical Center, San Francisco, CA 94115. Abstract
broadcast on www.provet.co.uk
|
This information is provided by
Provet for educational purposes only.
You should seek the advice of your
veterinarian if your pet is ill as only he or she can correctly advise on the
diagnosis and recommend the treatment that is most appropriate for your pet.
Abstract
Mammalian cells can respond to damage or stress by entering a state of
arrested growth and altered function termed cellular senescence. Several lines
of evidence suggest that the senescence response suppresses tumorigenesis.
Cellular senescence is also thought to contribute to aging, but the mechanism
is not well understood. We show that senescent human fibroblasts stimulate
premalignant and malignant, but not normal, epithelial cells to proliferate in
culture and form tumors in mice. In culture, the growth stimulation was
evident when senescent cells comprised only 10% of the fibroblast population
and was equally robust whether senescence was induced by replicative
exhaustion, oncogenic RAS, p14(ARF), or hydrogen peroxide. Moreover, it was
due at least in part to soluble and insoluble factors secreted by senescent
cells. In mice, senescent, much more than presenescent, fibroblasts caused
premalignant and malignant epithelial cells to form tumors. Our findings
suggest that, although cellular senescence suppresses tumorigenesis early in
life, it may promote cancer in aged organisms, suggesting it is an example of
evolutionary antagonistic pleiotropy.
Reference
Proc Natl Acad Sci U S A 2001 Oct 9;98(21):12072-7
Updated January 2016
|