Journal de recherche et de thérapie sur les cellules souches

Abstrait

Reprogramming Cancer Cells In Vivo

Brian W. Booth, Sonia M Rosenfield and Gilbert H Smith

Tissue microenvironments have tremendous influence on both local cells and the surrounding tissues. Signals originating from the local microenvironment, both chemical and physical, help to regulate cell and tissue functions including proliferation, differentiation, wound healing, and tumorigenesis. Tumorigenesis is often defined as the result of multiple mutations that provide a growth advantage and lead to clonal expansion of a mutated population. Evidence is accumulating that demonstrates that local microenvironment impacts the behavior of cancer cells by favoring or inhibiting tumor progression. This review will discuss studies that demonstrate the potential of the mouse mammary microenvironment to reprogram tumor-derived cells into cells that contribute to the formation of a functional, tumorfree, mammary outgrowth. Mouse and human tumor cells, derived from different species and tumor types, are incorporated into regenerating mammary structures and differentiate in luminal, myoepithelial, and milk producing secretory cells when incorporated into a competent mammary niche. These findings demonstrate that human or mouse cancers independent of their origin or differentiation state retain a subpopulation of cells with stem/progenitor activity that respond to the signals of a normal microenvironment and contribute their progeny to normal development, which suppresses their malignant phenotype. During this process, the normal mouse mammary cells are able to supply paracrine signals necessary for normal mammary gland development such as steroid receptor signals that the human and mouse cancer cells cannot.