Senescent fibroblasts in melanoma initiation and progression: an integrated theoretical, experimental, and clinical approach.

ABSTRACT: We present an integrated study to understand the key role of senescent fibroblasts in driving melanoma progression. Based on the hybrid cellular automata paradigm, we developed an in silico model of normal skin. The model focuses on key cellular and microenvironmental variables that regulate interactions among keratinocytes, melanocytes, and fibroblasts, key components of the skin. The model recapitulates normal skin structure and is robust enough to withstand physical as well as biochemical perturbations. Furthermore, the model predicted the important role of the skin microenvironment in melanoma initiation and progression. Our in vitro experiments showed that dermal fibroblasts, which are an important source of growth factors in the skin, adopt a secretory phenotype that facilitates canc

SUBMITTER: Kim E 

PROVIDER: S-EPMC3926439 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature