A novel neuregulin – jagged1 paracrine loop in breast cancer transendothelial migration

Cabrera, Ramon M.; Mao, S.; Surve, Chinmay R.; Condeelis, John S.; Segall, Jeffrey E.

doi:10.1186/s13058-018-0960-8

Cited by 23 publications

(23 citation statements)

References 42 publications

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“…Activation of the Notch signaling pathway upregulates E-selectin expression on endothelial cells that shields tumor cells in the blood stream from anoikis (112). In breast cancer models, inhibition of the Notch signaling pathway blocked macrophage-induced intravasation in vitro and the dissemination of tumor cells from the primary tumor in vivo (113). The association between EMT and radioresistance and the prominent role of Notch signaling as a driving force in the EMT process, suggest that Notch inhibition will result in radiosensitization of tumors that underwent EMT.…”

Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

“…Targeting the fibrotic TME can be challenging. Kalluri et al found that when myofibroblasts were eliminated from the TME using transgenic mice, cancer progression and outcome were worse (113). Deletion of myofibroblasts was also associated with a reduced Teff/Treg ratio and elevated CTLA-4 expression (113).…”

Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

“…Kalluri et al found that when myofibroblasts were eliminated from the TME using transgenic mice, cancer progression and outcome were worse (113). Deletion of myofibroblasts was also associated with a reduced Teff/Treg ratio and elevated CTLA-4 expression (113). This could be because certain structure is needed to allow for normal functioning of immune cells and to keep the tumor in place.…”

Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

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Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment

2019

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Radiation therapy has been used for many years to treat tumors based on its DNA-damage-mediated ability to kill cells. More recently, RT has been shown to exert beneficial modulatory effects on immune responses, such as triggering immunogenic cell death, enhancing antigen presentation, and activating cytotoxic T cells. Consequently, combining radiation therapy with immunotherapy represents an important area of research. Thus far, immune-checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been the focus of many research studies and clinical trials. The available data suggest that such immunotherapies are enhanced when combined with radiation therapy. However, treatment resistance, intrinsic or acquired, is still prevalent. Various theories as to how to enhance these combination therapies to overcome treatment resistance have been proposed. In this review, we focus on the principles surrounding radiation therapy's positive and negative effects on the tumor microenvironment. We explore mechanisms underlying radiation therapy's synergistic and antagonistic effects on immune responses and provide a base of knowledge for radio-immunology combination therapies to overcome treatment resistance. We provide evidence for targeting regulatory T cells, tumor-associated macrophages, and cancer-associated fibroblasts in combination radio-immunotherapies to improve cancer treatment.

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Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

Section: Rt's Remodeling Of the Extracellular Matrix And Endothelial mentioning

confidence: 99%

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Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment

2019

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“…For example, in a study of basal-like BC cells it was found that lipopolysaccharide (LPS) treatment of macrophages induced the expression of Jag1 in these cells; based on other findings provided in that study, the authors suggested that through such Jag1 up-regulation the macrophages could have led to Notch activation in cancer stem cells (CSCs) and then to their expansion [ 88 ] ( Figure 1 (A2)). In another study, it was found that TNBC cells expressed neuregulin 1 (NRG1) that activated macrophage-expressed ErbB3, leading to increased expression of Jag1 by the macrophages; then, when the two cells interacted in co-culture, Jag1 was necessary for induction of tumor cell trans-endothelial migration (presumably by binding to cancer cell-expressed Notch) [ 89 ].…”

Section: Network No 1: Cross-talks Of the Notch Pathway With Myelmentioning

confidence: 99%

Notch-Inflammation Networks in Regulation of Breast Cancer Progression

Liubomirski

Ben‐Baruch

2020

Cells

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Members of the Notch family and chronic inflammation were each separately demonstrated to have prominent malignancy-supporting roles in breast cancer. Recent investigations indicate that bi-directional interactions that exist between these two pathways promote the malignancy phenotype of breast tumor cells and of their tumor microenvironment. In this review article, we demonstrate the importance of Notch-inflammation interplays in malignancy by describing three key networks that act in breast cancer and their impacts on functions that contribute to disease progression: (1) Cross-talks of the Notch pathway with myeloid cells that are important players in cancer-related inflammation, focusing mainly on macrophages; (2) Cross-talks of the Notch pathway with pro-inflammatory factors, exemplified mainly by Notch interactions with interleukin 6 and its downstream pathways (STAT3); (3) Cross-talks of the Notch pathway with typical inflammatory transcription factors, primarily NF-κB. These three networks enhance tumor-promoting functions in different breast tumor subtypes and act in reciprocal manners, whereby Notch family members activate inflammatory elements and vice versa. These characteristics illustrate the fundamental roles played by Notch-inflammation interactions in elevating breast cancer progression and propose that joint targeting of both pathways together may provide more effective and less toxic treatment approaches in this disease.

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“…NRG-1 treatment induced cancer stem cell (CSC) characteristics in breast cancer (BC) cell lines in vitro [51]. Furthermore, NRG-1 produced by BC cells can enhance transendothelial migration and intravasation, due to induction of jagged-1 (JAG1), an important component of the Notch pathway [52]. In BC, NRG-1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-[53] overexpressing breast cancer cells [54].…”

Section: Neuregulin-1 In Diseasementioning

confidence: 99%