Adipocyte biology in breast cancer: From silent bystander to active facilitator

Choi, Jong Myung; Jin, Yoon; Koo, Ja Seung

doi:10.1016/j.plipres.2017.11.002

Cited by 202 publications

(196 citation statements)

References 171 publications

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“…Pericytes also contribute to angiogenesis and confer resistance to antiangiogenic therapy 11,12 . Adipocytes support cancers mainly through the secretion of growth factors and cytokines, and have also been shown to have roles in resistance to chemotherapies, radiotherapy, hormone therapy, and targeted therapies 13 . Immune cells influence protumorigenic phenotypes (epithelial-to-mesenchymal transition, angiogenesis, and therapy resistance) and antitumour phenotypes (immune surveillance) through diverse and complex mechanisms 11,14–16 .…”

Section: Components Of the Stromamentioning

confidence: 99%

Targeting the tumour stroma to improve cancer therapy

2018

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Cancers are not merely composed of cancer cells alone and, instead, are complex ‘ecosystems’ comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistroma agents. Herein, we provide an overview of the advances in understanding the complex cancer cell–tumour stroma interactions, and discuss how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes.

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Section: Components Of the Stromamentioning

confidence: 99%

Targeting the tumour stroma to improve cancer therapy

2018

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“…Cancer cell proliferation and migration is induced by activated fibroblasts derived from endothelial-to-mesenchymal transformation 64 . The cancer associated adipocytes (CAAs) have a significant role in cancer progression, ECM remodeling, phenotype changes of CAFs, and resistance to cancer therapy 65 . They show tumor-modified phenotype with ability to modify cancer cell phenotype favoring metastasis 66 .…”

Section: Introductionmentioning

confidence: 99%

Role of extracellular matrix in breast cancer development: a brief update

Jena

Janjanam²

2018

F1000Res

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Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

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“…Here, we studied leptin, a hormone primarily secreted by adipocytes, which is also secreted, in lesser extent, in normal and tumorigenic mammary tissue [80,81]. Several studies have established the association between overexpression of leptin and its receptor, ObR, during breast cancer progression [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

“…Leptin plays an important role in the regulation of energy homeostasis, endocrine and immune functions, as well as in lipid and glycolytic metabolism [2,3]. The overexpression of leptin and its receptor, the ObR, has been associated to tumor progressionrelated events in breast cancer [4][5][6]. Leptin exerts its effects through binding with the ObR receptor, promoting the activation of several signaling pathways such as MAPK, PI3K/AKT and JAK/STAT [3,7,8].…”

Section: Introductionmentioning

confidence: 99%

Leptin promotes expression of EMT-related transcription factors and invasion in a Src and FAK-dependent pathway in MCF10A mammary epithelial cells

Olea-Flores

Zuñiga-Eulogio

Tacuba-Saavedra

et al. 2019

Preprint

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Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these kinases using an in vitro model for leptin-induced EMT process in the non-tumorigenic MCF10A cell line. To this end, MCF10A cells were stimulated with leptin, and Src and FAK activation was assessed. Specific events occurring during EMT were also evaluated in the presence or absence of the kinases's chemical inhibitors PP2 and PF-573228. For instance, we tested the expression and subcellular localization of the EMT--catenin, by western blot and immunofluorescence. We also evaluated the secretion and activation of matrix metalloproteases (MMP-2 and MMP-9) by gelatin zymography. Invasiveness properties of leptin-stimulated cells were determined by invadopodia formation assays, and by the transwell chamber method. Our results showed that leptin promotes EMT through Src and FAK activation, which leads to the secretion and activation of MMP-2 and MMP-9, invadopodia formation and cell invasion in MCF10A cells. In conclusion, our data suggest that -catenin, the secretion of MMP-2, MMP-9, the invadopodia formation and invasion in MCF10A cells in a Src and FAK-dependent manner.

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Adipocyte biology in breast cancer: From silent bystander to active facilitator

Cited by 202 publications

References 171 publications

Targeting the tumour stroma to improve cancer therapy

Targeting the tumour stroma to improve cancer therapy

Role of extracellular matrix in breast cancer development: a brief update

Leptin promotes expression of EMT-related transcription factors and invasion in a Src and FAK-dependent pathway in MCF10A mammary epithelial cells

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