Epithelial Cells and Their Neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer

Abstract

Intestinal myofibroblasts are ␣-smooth muscle actin-positive stromal cells that exist as a syncytium with fibroblasts and mural cells in the lamina propria of the gut. Through expression and secretion of cytokines, chemokines, growth factors, prostaglandins, and basal lamina/extracellular matrix molecules, as well as expression of adhesion molecules and receptors for many of the same soluble factors and matrix, myofibroblasts mediate information flow between the epithelium and the mesenchymal elements of the lamina propria. With the use of these factors and receptors, they play a fundamental role in intestinal organogenesis and in the repair of wounding or disease.Intestinal neoplasms enlist and conscript myofibroblast factors and matrix molecules to promote neoplastic growth, carcinoma invasion, and distant metastases.

Stromal myofibroblasts are drivers of invasive cancer growth

“…Coreceptors like heparan sulfate and decorin facilitate myofibroblast triggering by TGF-b. 10 In the adult, the stroma present in invasive tumors consists of both bone marrow-derived and non-bone marrow-derived myofibroblasts. Bone marrow-derived myofibroblasts originate either from circulating mesenchymal stem cells (MSC's) or CD341 fibrocytes (which have CD141 monocytes as precursor).…”

“…Some normal tissues, such as the gastro-intestinal tract and the lungs, also harbor myofibroblasts. 10,11 Besides their role in wound healing, myofibroblasts are essential for tissue morphogenesis, assist at stem cell niches and at mucosal immunity. 10,11 In cancer, a wound that does not heal, 12 myofibroblasts are either deficient or fullfil other functions such as the production of proinvasive proteinases.…”

“…10,11 Besides their role in wound healing, myofibroblasts are essential for tissue morphogenesis, assist at stem cell niches and at mucosal immunity. 10,11 In cancer, a wound that does not heal, 12 myofibroblasts are either deficient or fullfil other functions such as the production of proinvasive proteinases. 13 Early evidence in favor of a role for myofibroblasts in invasion was obtained by Dimanche-Boitrel et al 14 using a chemically induced rat colon cancer.…”

The Extracellular Matrix in Digestive Cancer

“…Given that the BM exists as an interface between tissues of endodermal and mesodermal origin it is not surprising that the intestinal BM itself has a dual origin, from both intestinal epithelial and mesenchymal cells [13,25,26]. Mesenchymal intestinal subepithelial myofibroblasts produce the majority of the BM's type IV collagen and entactin [13,27]. Laminin is produced commensurately by epithelial and mesenchymal cells and perlecan primarily from the epithelial compartment [13,27].…”

“…Mesenchymal intestinal subepithelial myofibroblasts produce the majority of the BM's type IV collagen and entactin [13,27]. Laminin is produced commensurately by epithelial and mesenchymal cells and perlecan primarily from the epithelial compartment [13,27].…”