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

Abstract

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. 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.