Abstract:
:During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that these senescence-related active fibroblasts can dedifferentiate proliferating primary human luminal cells to multipotent stem cells in an interleukin-8 (IL-8)-dependent manner. This was confirmed using recombinant IL-8, while the truncated protein was not active. This IL-8-related dedifferentiation of luminal cells was mediated through the STAT3-dependent downregulation of p16INK4A and the microRNA miR-141. Importantly, these in vitro-generated mammary stem cells exhibited high molecular and cellular similarities to human mammary stem cells. They have also shown a long-term mammary gland-reconstituting ability and the capacity to produce milk postdelivery. Thereby, these IL-8-generated mammary stem cells could be of great value for autologous cell therapy procedures and also for biomedical research as well as drug development.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Al-Khalaf HH,Ghebeh H,Wakil SM,Al-Mohanna F,Aboussekhra Adoi
10.1128/MCB.00508-19subject
Has Abstractpub_date
2020-04-13 00:00:00issue
9eissn
0270-7306issn
1098-5549pii
MCB.00508-19journal_volume
40pub_type
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