Fibroblast Subsets in Intestinal Homeostasis, Carcinogenesis, Tumor Progression, and Metastasis

Abstract

In intestinal homeostasis, continuous renewal of the epithelium is crucial to withstand the plethora of stimuli which can damage the structural integrity of the intestines. Fibroblasts contribute to this renewal by facilitating epithelial cell differentiation as well as providing the structural framework in which epithelial cells can regenerate. Upon dysregulation of intestinal homeostasis, (pre-) malignant neoplasms develop, a process which is accompanied by (epi) genetic alterations in epithelial cells as well as phenotypic changes in fibroblast populations. In the context of invasive carcinomas, these fibroblast populations are termed cancer-associated fibroblasts (CAFs). CAFs are the most abundant cell type in the tumor microenvironment of colorectal cancer (CRC) and consist of various functionally heterogeneous subsets which can promote or restrain cancer progression. Although most previous research has focused on the biology of epithelial cells, accumulating evidence shows that certain fibroblast subsets can also importantly contribute to tumor initiation and progression, thereby possibly providing avenues for improvement of clinical care for CRC patients. In this review, we summarized the current literature on the emerging role of fibroblasts in various stages of CRC development, ranging from adenoma initiation to the metastatic spread of cancer cells. In addition, we highlighted translational and therapeutic perspectives of fibroblasts in the different stages of intestinal tumor progression.

Facile preparation of aqueous-soluble fluorescent polyethylene glycol functionalized carbon dots from palm waste by one-pot hydrothermal carbonization for colon cancer nanotheranostics

“…Colon cancer cells (CaCo-2) and Fibroblast were chosen as the cancer model and the normal cell control, respectively. From recent studies, there was clear evidence that cancer-associated fibroblasts (CAFs) play a crucial role in intestinal tumor 71 as well as colon cancer cells progression 72 . Fibroblasts were found to surround tumor cells and consist of various heterogeneous subsets which can exert both tumor-promoting and -suppressing functions 73 , hence they were selected as normal cell control in the present study.…”

Study of the colonic epithelial-mesenchymal dialogue through establishment of two activated or not mesenchymal cell lines: Activated and resting ones differentially modulate colonocytes in co-culture

“…They will also be of considerable interest to experimentally determine the pathways leading to CRC development and to identify potential molecular targets for cancer prevention. Indeed, although CCR develops from crypt epithelial cells, the proliferation regulation of these cells and the microenvironment modification induced by fibroblasts may play an important role in disease progression [ 50 ]. All these data allow us to conclude that the mF lineage is representative of activated fibroblastic cells that could be encountered in pathological situations and is therefore of major interest in coculture systems aiming to determine the role of mesenchyme in the development of intestinal pathologies.…”

Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization

“…Underlying the intestinal epithelium, fibroblasts and myofibroblasts are present as part of the mesenchymal cell population in the submucosa. Fibroblasts secrete extracellular matrix components that can ameliorate epithelial cell morphology and maintain the structural integrity of the intestinal mucosa (Dang et al., 2021; Darling et al., 2020). Fibroblasts also regulate the proliferation and differentiation of intestinal epithelial stem cells via paracrine action (Göke et al., 1998), as well as immune cell homeostasis, through the secretion of IL‐6 and CCL2 and through the direct interaction with immune cells (Dang et al., 2021).…”

“…Fibroblasts secrete extracellular matrix components that can ameliorate epithelial cell morphology and maintain the structural integrity of the intestinal mucosa (Dang et al., 2021; Darling et al., 2020). Fibroblasts also regulate the proliferation and differentiation of intestinal epithelial stem cells via paracrine action (Göke et al., 1998), as well as immune cell homeostasis, through the secretion of IL‐6 and CCL2 and through the direct interaction with immune cells (Dang et al., 2021). A direct relationship between fibroblast function and the allergic sensitization pathway has not been described.…”