Fibroblast Stimulation of Blood Vessel Development and Cancer Cell Invasion in a Subrenal Capsule Xenograft Model: Stress-Induced Premature Senescence Does Not Increase Effect

Abstract

Fibroblast cooperation with cancer cells in xenograft development was investigated by transplanting MDAMB-231 cells under the kidney capsule of immunodeficient mice. Control fibroblasts and fibroblasts subjected to stress-induced premature senescence by treatment with bleomycin were used. In other xenograft models, senescent fibroblasts have shown a growth-stimulatory effect greater than that of control cells. In this model, both types of fibroblasts accelerated the formation and growth of xenografts. Blood vessel development, as evidence by von Willebrand factor staining, was greatly accelerated by the presence of fibroblasts, and invasion into the kidney was also increased. Control and senescent fibroblasts had very similar effects. These actions of fibroblasts were partially recapitulated in in vitro experiments. Both control and senescent fibroblasts stimulated the tubulogenesis of endothelial cells in culture and stimulated the invasion of MDA-MB-231 cells through Matrigel in vitro. In this xenograft model, in which fibroblasts are cotransplanted with a cancer cell into an internal organ rather than subcutaneously, senescence was not an important factor in the effects of cotransplanted fibroblasts on growth, blood vessel development, and invasion. Therefore, cancer promotion by the senescence of adjacent stromal cells may be restricted to certain organ and tissue types.

Keywords

• Senescence
• cancer cell xenografts
• immunodeficient mice
• stroma
• subrenal capsule