Mesenchymal Cells in Colon Cancer

Abstract

Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer. Mesenchymal cells in tumors, called cancer-associated fibroblasts, arise via activation of resident mesenchymal cell populations and the recruitment of bone marrow-derived mesenchymal stem cells and fibrocytes. Cancer-associated fibroblasts have a variety of activities that promote colon tumor development and progression; these include regulation of intestinal inflammation, epithelial proliferation, stem cell maintenance, angiogenesis, extracellular matrix remodeling, and metastasis. We review the intestinal mesenchymal cell-specific pathways that regulate these processes, with a focus on their roles in mediating interactions between inflammation and carcinogenesis. We also discuss how increasing our understanding of intestinal mesenchymal cell biology and function could lead to new strategies to identify and treat colitis-associated cancers.

Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

“…Tumors cells may support tumor growth by educating the surrounding fibroblasts, which are referred to as CAFs 8, 37, 38 . On the other hand, a recent study reported that surface expression of CD10 and GPR77 may be markers of CAFs that mediate chemotherapy resistance in human cancer through IL-6 and IL-8 production 10 .…”

“…These stromal cells organize the tissue architecture, and have recently been revealed to play crucial roles in regulating immune responses, tissue repair, and tumor development 3,4,5 . Recent studies have focused on fibroblasts that can support tumor growth, termed cancer-associated fibroblasts (CAFs) 6,7,8 . In a very recent study, single-cell RNA-sequencing (scRNA-seq) was performed to analyze colon biopsies from healthy individuals and ulcerative colitis (UC) patients.…”

Next-generation sequencing traces human induced pluripotent stem cell lines clonally generated from heterogeneous cancer tissue

“…Accordingly, materials and methods can be optimized to generate normal or aberrant iPSC lines for the purposes of regenerative medicine or cancer research/therapy. Cancer tissues comprise (pre-) cancer (stem) cells, pre-metastatic cancer cells, stromal cells (such as mesenchymal stem cells, cancer-associated fibroblasts[15,16,24] and tumor endothelial cells) and immune cells (such as tumor-associated macrophages[25], dendritic cells[26] and tumor-infiltrating T cells[23]). Therefore, such a cell-derived iPSC line might be useful for immune-cell therapy[27] with cellular vaccines[28], dendritic cells[29-32] or tumor antigen-specific cytotoxic T cells[23], in addition to the development of models of carcinogenesis[33-35] and drug discovery tools[36,37].…”

Linking Race, Cancer Outcomes, and Tissue Repair

“…The American Journal of Pathologyajp.amjpathol.org cancer. 107 Recent studies are beginning to suggest possible differences in the activation of stem cellelike self-renewal pathways in colon cancer based on race with a focus on the role of specific microRNAs. 108e111 Like breast cancer, recent studies are beginning to reveal differential signatures and influences of inflammatory pathways in prostate cancer 112e114 and the role of EMT in the generation and support of the stem cell niche.…”