Tumor-stroma interactions

Vanderbilt University, Нашвилл, Michigan, United States
Current Opinion in Genetics & Development (Impact Factor: 7.57). 03/2005; 15(1):97-101. DOI: 10.1016/j.gde.2004.12.003
Source: PubMed


The importance of stromal cells and the factors that they express during cancer initiation and progression has been highlighted by recent literature. The cellular components of the stroma of epithelial tissues are well-recognized as having a supportive role in carcinogenesis, where the initiating mutations of a tumor originate in the epithelial cells. The use of mouse models and xenografts suggests that mutations in the stromal fibroblasts can also initiate epithelial tumors. Many of these tumors result from the alteration of paracrine growth factor pathways that act on the epithelia. However, the tissue specificity of the responses to the growth factors is a mystery not yet solved.

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    • "Biological and ecological processes often involve moving fronts of interacting subpopulations. For example, in a biological setting, malignant spreading occurs when tumour cells interact with, and move through, the stroma (Bhowmick and Moses, 2005; De Wever and Mareel, 2003; Gatenby et al., 2006; Li et al., 2003). In an ecological setting, the spreading of an invasive species involves moving fronts, that, in some cases, is coupled with a retreating front of that species' prey (Hastings et al., 2005; Phillips et al., 2007; Skellam, 1951). "
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    ABSTRACT: Mathematical models describing the movement of multiple interacting subpopulations are relevant to many biological and ecological processes. Standard mean-field partial differential equation descriptions of these processes suffer from the limitation that they implicitly neglect to incorporate the impact of spatial correlations and clustering. To overcome this, we derive a moment dynamics description of a discrete stochastic process which describes the spreading of distinct interacting subpopulations. In particular, we motivate our model by mimicking the geometry of two typical cell biology experiments. Comparing the performance of the moment dynamics model with a traditional mean-field model confirms that the moment dynamics approach always outperforms the traditional mean-field approach. To provide more general insight we summarise the performance of the moment dynamics model and the traditional mean-field model over a wide range of parameter regimes. These results help distinguish between those situations where spatial correlation effects are sufficiently strong, such that a moment dynamics model is required, from other situations where spatial correlation effects are sufficiently weak, such that a traditional mean-field model is adequate.
    Preview · Article · Jan 2015 · Journal of Theoretical Biology
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    • "During the progression of breast carcinomas the epithelial cells as well as the cells of the stroma increase the synthesis of ECM components, resulting in changes in the composition and thereby structure of the matrix [9], as illustrated by histological and biochemical studies [10] [11] [12] [13] [14]. Notably, the tumor stroma resembles the stroma during embryonic development, which is rich in glycosaminoglycans and promotes cellular proliferation and migration [1] [15]. "
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    ABSTRACT: Background The progression of cancer through stages that guide a benign hyperplastic epithelial tissue towards a fully malignant and metastatic carcinoma, is driven by genetic and microenvironmental factors that remodel the tissue architecture. The concept of epithelial-mesenchymal transition (EMT) has evolved to emphasize the importance of plastic changes in tissue architecture, and the cross-communication of tumor cells with various cells in the stroma and with specific molecules in the extracellular matrix (ECM). Scope of the review Among the multitude of ECM-embedded cytokines and the regulatory potential of ECM molecules, this article focuses on the cytokine transforming growth factor β (TGFβ) and the glycosaminoglycan hyaluronan, and their roles in cancer biology and EMT. For brevity, we concentrate our effort on breast cancer. Major conclusions Both normal and abnormal TGFβ signaling can be detected in carcinoma and stromal cells, and TGFβ-induced EMT requires the expression of hyaluronan synthase 2 (HAS2). Correspondingly, hyaluronan is a major constituent of tumor ECM and aberrant levels of both hyaluronan and TGFβ are thought to promote a wounding reaction to the local tissue homeostasis. The link between EMT and metastasis also involves the mesenchymal-epithelial transition (MET). ECM components, signaling networks, regulatory non-coding RNAs and epigenetic mechanisms form the network of regulation during EMT-MET. General significance Understanding the mechanism that control epithelial plasticity in the mammary gland promises the development of valuable biomarkers for the prognosis of breast cancer progression and even provides new ideas for a more integrative therapeutic approach against disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
    Full-text · Article · Aug 2014 · Biochimica et Biophysica Acta (BBA) - General Subjects
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    • "Release of pro-inflammatory mediators and increased local levels of oxygen and nitrogen species can contribute to carcinogenesis [5]. The dysregulated production of cytokines in inflammatory microenvironment stimulates the expression of genes associated with cancer development and modifies structural features of microenvironment to accelerate cancer initiation and progression [6]–[9]. "
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    ABSTRACT: Accumulating evidence indicate that macrophages activate mesenchymal stem cells (MSCs) to acquire pro-inflammatory phenotype. However, the role of MSCs activated by macrophages in gastric cancer remains largely unknown. In this study, we found that MSCs were activated by macrophages to produce increased levels of inflammatory cytokines. Cell colony formation and transwell migration assays revealed that supernatants from the activated MSCs could promote both gastric epithelial cell and gastric cancer cell proliferation and migration. In addition, the expression of epithelial-mesenchymal transition (EMT), angiogenesis, and stemness-related genes was increased in activated MSCs. The phosphorylated forms of NF-κB, ERK and STAT3 in gastric cells were increased by active MSCs. Inhibition of NF-κB activation by PDTC blocked the effect of activated MSCs on gastric cancer cells. Co-injection of activated MSCs with gastric cancer cells could accelerate gastric cancer growth. Moreover, human peripheral blood monocytes derived macrophages also activated MSCs to prompt gastric cancer cell proliferation and migration. Taken together, our findings suggest that MSCs activated by macrophage acquire pro-inflammatory phenotype and prompt gastric cancer growth in an NF-κB-dependent manner, which provides new evidence for the modulation of MSCs by tumor microenvironment and further insight to the role of stromal cells in gastric carcinogenesis and cancer progression.
    Full-text · Article · May 2014 · PLoS ONE
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