Reversing the aging stromal phenotype prevents carcinoma initiation

Davina A. Lewis, Jeffrey Travers, Christiane Machado, Ally-Khan Somani, Dan Spandau

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The accumulation of senescent stromal cells in aging tissue changes the local microenvironment from normal to a state similar to chronic inflammation. This inflammatory microenvironment can stimulate the proliferation of epithelial cells containing DNA mutations which can ultimately lead to cancer. Using geriatric skin as a model, we demonstrated that senescent fibroblasts also alter how epithelial keratinocytes respond to genotoxic stress, due to the silencing of IGF-1 expression in geriatric fibroblasts. These data indicate that in addition to promoting epithelial tumor growth, senescent fibroblasts also can promote carcinogenic initiation. We hypothesized that commonly used therapeutic stromal wounding therapies can reduce the percentage of senescent fibroblasts and consequently prevent the formation of keratinocytes proliferating with DNA mutations following acute genotoxic (UVB) stress. Sun-protected skin on the lower back of geriatric human volunteers was wounded by dermabrasion and the skin was allowed to heal for three months. In geriatric skin, we found that dermabrasion wounding decreases the proportion of senescent fibroblasts found in geriatric dermis, increases the expression of IGF-1, and restores the appropriate UVB response to epidermal keratinocytes in geriatric skin. Therefore, dermal rejuvenation therapies may play a significant role in preventing the initiation of skin cancer in geriatric patients.

Original languageEnglish
Pages (from-to)407-416
Number of pages10
JournalAging
Volume3
Issue number4
StatePublished - Apr 2011

Fingerprint

Geriatrics
Carcinoma
Phenotype
Fibroblasts
Skin
Dermabrasion
Keratinocytes
Insulin-Like Growth Factor I
DNA Damage
Play Therapy
Rejuvenation
Mutation
Cell Aging
DNA
Skin Neoplasms
Solar System
Dermis
Stromal Cells
Volunteers
Neoplasms

Keywords

  • Aging
  • Photocarcinogenesis
  • Senescence
  • Therapy
  • UVB

ASJC Scopus subject areas

  • Aging
  • Cell Biology
  • Geriatrics and Gerontology

Cite this

Reversing the aging stromal phenotype prevents carcinoma initiation. / Lewis, Davina A.; Travers, Jeffrey; Machado, Christiane; Somani, Ally-Khan; Spandau, Dan.

In: Aging, Vol. 3, No. 4, 04.2011, p. 407-416.

Research output: Contribution to journalArticle

Lewis, Davina A. ; Travers, Jeffrey ; Machado, Christiane ; Somani, Ally-Khan ; Spandau, Dan. / Reversing the aging stromal phenotype prevents carcinoma initiation. In: Aging. 2011 ; Vol. 3, No. 4. pp. 407-416.
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