The Stromal Niche for Epithelial Stem Cells: A Template for Regeneration and a Brake on Malignancy

Stromal restraint of cancer growth and progression—emerging as a widespread phenomenon in epithelial cancers such as bladder, pancreas, colon, and prostate—appears rooted in stromal cell niche activity. During normal tissue repair, stromal niche signals, often Hedgehog-induced, promote epithelial stem cell differentiation as well as self-renewal, thus specifying a regenerating epithelial pattern. In the case of cancerous tissue, stromal cell-derived differentiation signals in particular may provide a brake on malignant growth. Understanding and therapeutic harnessing of the role of stroma in cancer restraint may hinge on our knowledge of the signaling programs elaborated by the stromal niche.