The role of interleukin-1 in interactive senescence and age-related human endometrial cancer

The causes of the age-related increase in cancer rates are poorly understoo d. One cause could be age-related changes in the stromal/epithelial cell in teractions that facilitate tumorigenesis, We tested the hypothesis that agi ng of human endometrial stromal fibroblasts (ESF) alters their influence ov er endometrial epithelial cells, ESF from adults were found to inhibit anch orage-independent proliferation, to restrain colony outgrowth, and to induc e formation of normal tissue architecture by human endometrial cancer cells . As ESF age, these inhibitory influences on malignant-like behaviors by ep ithelial cells are altered, becoming stimulatory, Age-related change in int erleubin-1 alpha (IL-1 alpha) expression is a molecular determinant of ESF/ epithelial cell interactions. Levels of IL-1 alpha and IL-1-induced mRNAs i ncrease in ESF with age, Treatment with IL-1 accelerates age-related change s in mRNA abundance and loss of ESF restraint over malignancy-associated be haviors by epithelial cells, Transfection of ESF with the intracellular IL- 1 receptor antagonist preserved the young phenotype with respect to interac tions with epithelial cells and prevented age-associated increases in gro a lpha and IL-8 mRNA levels, Our results indicate that aging of ESF is accomp anied by an interactive senescence that alters ESF signaling to cancer cell s and could contribute to increased cancer rates by providing a microenviro nment that is more conducive to tumorigenesis, (C) 1999 Academic Press.