Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer

Jung, Yoon Yang; Lee, Yu Kyung; Koo, Ja Seung

doi:10.1007/s13277-015-3594-9

Cited by 35 publications

(24 citation statements)

References 36 publications

(39 reference statements)

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“…CAF markers, in contrast, seem to display the opposite pattern of expression. Such observations are consistent with fibrosis in breast tumors, and with the higher incidence of tumors with adipose stroma among those of the Luminal A subtype (Jung et al, 2015). The change in stromal adipocyte content between normal breast and breast tumor is also apparent in H&E staining slides gathered from matched tumor/normal samples from TCGA (Figure 5c).…”

Section: Resultssupporting

confidence: 83%

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

et al. 2016

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Summary Cancer progression depends on both cell-intrinsic processes and interactions between different cell types. However, large scale assessment of cell type composition and molecular profiles of individual cell types within tumors remains challenging. To address this, we developed Epigenomic Deconvolution (EDec), an in silico method that infers cell type composition of complex tissues as well as DNA methylation and gene transcription profiles of constituent cell types. By applying EDec to The Cancer Genome Atlas (TCGA) breast tumors we detect changes in immune cell infiltration related to patient prognosis, and a striking change in stromal fibroblast to adipocyte ratio across breast cancer subtypes. We further show that a less adipose stroma tends to display lower levels of mitochondrial activity and to be associated with cancerous cells with higher levels of oxidative metabolism. These findings highlight the role of stromal composition in the metabolic coupling between distinct cell types within tumors.

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Section: Resultssupporting

confidence: 83%

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

et al. 2016

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“…Of interest, while the risk for breast cancer is increased for obese postmenopausal women, premenopausal obese women have a lower incidence of breast cancer (84). Adipocytes comprise about 90% of the normal breast tissue and thus, the question of adipocytes contributing directly to tumor progression as part of the tumor stroma has been addressed in several studies (66,68,70,75,76). Breast cancer stroma can be classified into adipose stroma cancer (>50% of cells are adipocytes), and fibrous stroma cancer (100% of cells are fibroblasts) or a combination of both stroma types (<100% of cells are fibroblasts, <50% are adipocytes) (76).…”

Section: Resultsmentioning

confidence: 99%

“…In a large study, n=939 breast cancer cases were classified depending on the adipose tissue and fibroblast content within the tumor stroma into adipose stroma type and fibrous stroma type (76). The differences between these two cancer types were investigated regarding the breast cancer subtypes, molecular tumor characteristics and the patients’ outcome (76).…”

Section: Resultsmentioning

confidence: 99%

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Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Himbert

Delphan

Scherer

et al. 2017

Cancer Prevention Research

155

131

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Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiological, clinical, and preclinical data suggest that within the growth-promoting, pro-inflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct “crosstalk” between adipose tissue and carcinomas in humans. We identified 4,641 articles with n=20 human clinical studies which are summarized as: (a) breast (n=7), (b) colorectal (n=4), (c) esophageal (n=2), (d) esophageal/colorectal (n=1), (e) endometrial (n=1), (f) prostate (n=4), and (g) ear-nose-throat (ENT) cancer (n=1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL-6, TNF-alpha and other mechanisms. Moreover, visceral white adipose tissue (VAT) plays a more central role as it is more bio-energetically active and is associated with a more pro-cancer secretome than subcutaneous adipose tissue (SAT). Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers.

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“…The tumor microenvironment is an important factor in cancer progression and EMT (23). Stromal cells are involved in the metastatic process and play a major role in promoting primary tumor growth.…”

Section: Snai2 Is Overexpressed In Aggressive Thyroid Cancer and Dirementioning

confidence: 99%

Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers

Boufraqech

Zhang

Nilubol

et al. 2016

Clinical Cancer Research

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Purpose: Epithelial-to-mesenchymal transition (EMT) is important in cancer progression and metastasis. We and others have previously reported that lysyl oxidase (LOX) is overexpressed in aggressive cancers, is associated with increased mortality, and regulates EMT. However, the mechanism by which LOX mediates EMT is unknown. In this study, we investigated the effect of LOX on mediators of EMT.Experimental Design: We used chromatin immunoprecipitation and promoter luciferase assays to determine the target gene of LOX. To determine the effects of SNAI2 in vivo, we used our metastatic anaplastic thyroid cancer (ATC) mouse model. To investigate the effects of LOX and SNAI2 on MMPs and TIMPs, protein arrays were used. Primary tumors from patients with metastatic, breast and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and TIMP4 expression by immunohistochemistry.Results: We found that LOX knockdown decreases SNAI2 expression in cancer cell lines. Furthermore, knockdown of LOX reduced SNAI2 expression in a metastatic mouse model of thyroid cancer. We also demonstrated that LOX binds and transactivates the SNAI2 promoter. We found a direct correlation in thyroid and breast cancer samples between LOX and SNAI2 expression. To understand how LOX/SNAI2 axis mediates these effects, we performed a comprehensive analysis of MMPs/TIMPs. LOX and SNAI2 depletion reduced TIMP4 secretion. Analysis of SNAI2 and TIMP4 expression showed overexpression of both proteins in aggressive thyroid, colon, and breast tumors.Conclusions: Our findings provide new evidence that LOX regulates SNAI2 expression and that SNAI2-mediated TIMP4 secretion plays a role in cancer progression.

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Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer

Cited by 35 publications

References 36 publications

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers

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