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. 2010 Mar 5;3(1):149-66.
doi: 10.1007/s12307-010-0038-3.

The tumor microenvironment in colorectal carcinogenesis

Vijay G Peddareddigari, Dingzhi Wang, Raymond N Dubois

The tumor microenvironment in colorectal carcinogenesis

Vijay G Peddareddigari et al. Cancer Microenviron. .

Abstract

Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Therapeutic developments in the past decade have extended life expectancy in patients with metastatic disease. However, metastatic colorectal cancers remain incurable. Numerous agents that were demonstrated to have significant antitumor activity in experimental models translated into disappointing results in extending patient survival. This has resulted in more attention being focused on the contribution of tumor microenvironment to the progression of a number of solid tumors including colorectal cancer. A more complete understanding of interactions between tumor epithelial cells and their stromal elements will enhance therapeutic options and improve clinical outcome. Here we will review the role of various stromal components in colorectal carcinogenesis and discuss the potential of targeting these components for the development of future therapeutic agents.

Keywords: Colon cancer; Extracellular matrix; Stroma; Tumor infiltrating cells; Tumor microenvironment.

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Figures

Fig. 1
Fig. 1
The models of a cross talk between transformed epithelial cells and stromal cells in promoting cancer progression. Following the initiation of epithelial tumors, the reciprocal interactions between transformed epithelial and stromal cells play a key role in switching a microenvironment from normal to one that supports tumor growth and spread. Tumor microenvironment, which is associated with massive infiltration of dysregulated immune cells as well as changes of their functionality, can promote tumor growth, angiogenesis, and metastasis. Tumor-infiltrating cells predominantly include tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), CD4 T-cells, CD8 T-cells, CD4 regulatory T-cells (Tregs), mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), endothelial progenitor cells (EPs), mast cells (MCs), and platelets (PLTs). These cells are able to maintain tumor associated inflammation, angiogenesis, and immunesuppression, which in turn promotes tumor growth and metastasis
Fig. 2
Fig. 2
Multiple functions of tumor-associated macrophages (TAMs). TAMs are one of the most important components of tumor stroma. M2 cells, differentiated TAM, facilitate tumor growth by contributing to tumor inflammation, angiogenesis, the epithelial-to-mesenchymal transition (EMT), tumor cell invasion, intravasation, extracellular matrix and matrix-associated molecule formation (ECM and MAM) as well as immunosuppression. They accomplish this by either direct contact with other cells or producing various growth factors, chemokines, and angiogenic factors such as inteleukin (IL)-10, IL-8, IL-6, IL-1β, prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), indoleamine dioxigenase (IDO), nitric oxide (NO), reactive oxygen intermediates (ROI), matrix metalloprotease (MMP)-2, MMP), epidermal growth factor (EGF), basic fibroblast growth factors (bFGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-β (PDGF-β). The figure depicts contributions of various TAM-derived factors to different processes
Fig. 3
Fig. 3
Roles of cancer-associated fibroblasts (CAFs) in colon carcinogenesis. CAFs are the chief constituent of tumor stroma. They facilitate tumor growth by secreting growth factors; promoting angiogenesis, tumor invasion, and metastasis; and are involved in the production of extracellular matrix (ECM) and matrix-associated molecules (MAMs). The figure depicts the contributions of various CAF-derived molecules. They include prostaglandin E2 (PGE2), transforming growth factor-β (TGF-β), matrix metalloprotease-2 (MMP2), epidermal growth factor (EGF), hepatocyte growth factor (HGF), basic fibroblast growth factors (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor-β (PDGF-β), secreted frizzled related protein (SFRP1), chemokine ligand 5 (CC5), osteopontin (OPN), and stromal cell-derived factor-1 (SDF-1), which is also called CXCL12
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References

    1. Whitlock EP, Lin JS, Liles E, et al. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149(9):638–658. - PubMed
    1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70. - PubMed
    1. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454(7203):436–444. - PubMed
    1. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–1081. - PubMed
    1. DuBois RN, Giardiello FM, Smalley WE. Nonsteroidal anti-inflammatory drugs, eicosanoids, and colorectal cancer prevention. Gastroenterol Clin North Am. 1996;25(4):773–791. - PubMed

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