Stromal fibroblasts in digestive cancer

Abstract

The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics.

Keywords: Bone-marrow derived cells; Cancer stroma; Digestive system neoplasms; Fibroblasts; Neoplasms.

Fig. 1

a Gastric cancer and b rectal adenoma in two female patients following male human allogeneic haematopoietic stem cell transplantation. Using Y-chr. CISH and α-SMA immunohistochemistry bone marrow derived α-SMA(+) gastric CAFs in A and ISEMFs in B (black arrows, reproduced with permission) [53]

Fig. 2

Schematic representation of the gastrointestinal stroma: the key stromal cells and events within the reactive stroma