Breast Tumor Microenvironment: Proteomics Highlights the Treatments Targeting Secretome

Chen, Shui Tein; Pan, Tai‐Long; Juan, Hsueh‐Fen; Chen, Tai-Yuan; Lin, Yih Shyan; Huang, Chun Ming

doi:10.1021/pr700745n

Cited by 59 publications

(52 citation statements)

References 104 publications

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“…Targeting FAP by developing more effective drugs based on proven anti-FAP compounds such as Sibrotuzumab (Kloft et al 2004) and PT-100 (Adams et al 2004) is one possible strategy. Of course, other pathways are also potential targets, such as those involved in attachment of cells to the ECM (Chen et al 2008), but it has also been shown that when integrins are reduced cells may adopt other modes of movement, such as swimming by shape changes (Renkawitz et al 2009;Renkawitz and Sixt 2010).…”

Section: Discussionmentioning

confidence: 99%

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A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

Kim

Othmer

2013

Bull Math Biol

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Ductal carcinoma in situ (DCIS) is an early stage noninvasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix (ECM) surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. Here we develop a mathematical model that incorporates the cross-talk between stromal and tumor cells, which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-β signaling pathways and show how upor down-regulation of components in these pathways affects cell growth and proliferation. We then study a hybrid model for the interaction of cells with the tumor microenvironment (TME), in which epithelial cells (ECs) are modeled individually while the ECM is treated as a continuum, and show how these interactions affect the early development of tumors. Finally, we incorporate breakdown of the epithelium into the model and predict the early stages of tumor invasion into the stroma. Our results shed light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.

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Section: Discussionmentioning

confidence: 99%

“…Several drugs targeting tumor associated fibroblasts (TAFs) or tumor associated macrophages (TAMs) have been developed (Chen et al 2008), but further modeling and computational analysis is needed to provide a basis for understanding optimal targets for preventing invasion.…”

Section: Discussionmentioning

confidence: 99%

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

Kim

Othmer

2013

Bull Math Biol

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“…Tumor cell moulds the microenvironment to support oncogenesis by releasing soluble and vesicular components, including enzymes, microvesicles, proteoglycans, chemokines, and cytokines (133). The tumor microenvironment components are shed into the circulation and may be extremely useful as an early diagnostic biomarker.…”

Section: Outlook-circulating Biomarkersmentioning

confidence: 99%

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

Shah

Saunders

Barbour

et al. 2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Esophageal adenocarcinoma (EAC) is one of the two most common types of esophageal cancer with alarming increase in incidence and very poor prognosis. Aiming to detect EAC early, currently high-risk patients are monitored using an endoscopic-biopsy approach. However, this approach is prone to sampling error and interobserver variability. Diagnostic tissue biomarkers related to genomic and cell-cycle abnormalities have shown promising results, although with current technology these tests are difficult to implement in the screening of high-risk patients for early neoplastic changes. Differential miRNA profiles and aberrant protein glycosylation in tissue samples have been reported to improve performance of existing tissue-based diagnostic biomarkers. In contrast to tissue biomarkers, circulating biomarkers are more amenable to population-screening strategies, due to the ease and low cost of testing. Studies have already shown altered circulating glycans and DNA methylation in BE/EAC, whereas disease-associated changes in circulating miRNA remain to be determined. Future research should focus on identification and validation of these circulating biomarkers in large-scale trials to develop in vitro diagnostic tools to screen population at risk for EAC development. Cancer Epidemiol Biomarkers Prev; 22(7); 1185-209. Ó2013 AACR.

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“…The changed (remodelled) microenvironment creates the elevated interstitial fluid pressure (IFP) creating chemoresistance. To improve the outcome of cancer therapy, researchers have developed several drugs targeting tumor associated fibroblasts (TAFs) or tumor associated macrophages (TAMs) [6]. The drugs targeting TAF include agents for Platelet-derived growth factor receptor (PDGFR) (Imatinib [39], SU11248 [32], BAY43-9006 [51], CDP860 [18]) and fibroblast activation protein (Sibrotuzumab [25], DNA vaccine, PT-100 [1]).…”

Section: Resultsmentioning

confidence: 99%

“…Understanding the relationship between tumor and its microenvironment may lead to important new therapeutic approaches in controlling the growth and metastasis of cancer. Indeed, instead of targeting the tumor cells, one may target stromal elements in order to manipulate the host-tumor interaction in a way that it will confine the tumor [6,31]. Thus, for instance, modulating cell adhesion or blocking Matrix Metalloproteinase (MMP) may be novel ways of confining cancer.…”

Section: Introductionmentioning

confidence: 99%

The role of the microenvironment in tumor invasion

Kim¹,

Lim²

2010

Proceedings of the 2009 SIAM Conference on “Mathematics for Industry”

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Fibroblasts and myofibroblasts in the tumor microenvironment are important players in tumor growth and metastasis because of their unique ability to coordinate events which increase cell proliferation and invasion especially in breast cancer. It has been experimentally shown that fibroblasts play an important role in promoting tumor growth. Our study illustrates a model in which tumor cells are able to communicate with these fibroblasts/myofibroblasts through proteinases for active invasion toward stroma near breast ducts.

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Breast Tumor Microenvironment: Proteomics Highlights the Treatments Targeting Secretome

Cited by 59 publications

References 104 publications

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

The role of the microenvironment in tumor invasion

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