scholarly journals GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis

Oncogene ◽  
2015 ◽  
Vol 34 (43) ◽  
pp. 5494-5504 ◽  
Author(s):  
G Maric ◽  
M G Annis ◽  
Z Dong ◽  
A A N Rose ◽  
S Ng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Integrin Α5β1 ◽  
Neuropilin 1 ◽  
Mammary Tumor Growth

Abstract 3293: Leptin induces breast cancer metastasis through a Neuropilin-1 (NRP-1)/OBR complex

2014 ◽  
Author(s):  
Zakia Belaid-Choucair ◽  
Julie Dam ◽  
Nicolas Goudin ◽  
Odile Filhole ◽  
Claude Cochet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Neuropilin 1

scholarly journals Obesity-Altered Adipose Stem Cells Promote ER+ Breast Cancer Metastasis through Estrogen Independent Pathways

2019 ◽  
Vol 20 (6) ◽  
pp. 1419 ◽  
Author(s):  
Rachel A. Sabol ◽  
Adam Beighley ◽  
Paulina Giacomelli ◽  
Rachel M. Wise ◽  
Mark A. A. Harrison ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Tumor Growth ◽  
Estrogen Receptor Alpha ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Adipose Stem Cells ◽  
Estrogen Signaling ◽  
Promote Tumor Growth

Adipose stem cells (ASCs) play an essential role in tumor microenvironments. These cells are altered by obesity (obASCs) and previous studies have shown that obASCs secrete higher levels of leptin. Increased leptin, which upregulates estrogen receptor alpha (ERα) and aromatase, enhances estrogen bioavailability and signaling in estrogen receptor positive (ER+) breast cancer (BC) tumor growth and metastasis. In this study, we evaluate the effect of obASCs on ER+BC outside of the ERα signaling axis using breast cancer models with constitutively active ERα resulting from clinically relevant mutations (Y537S and D538G). We found that while obASCs promote tumor growth and proliferation, it occurs mostly through abrogated estrogen signaling when BC has constitutive ER activity. However, obASCs have a similar promotion of metastasis irrespective of ER status, demonstrating that obASC promotion of metastasis may not be completely estrogen dependent. We found that obASCs upregulate two genes in both ER wild type (WT) and ER mutant (MUT) BC: SERPINE1 and ABCB1. This study demonstrates that obASCs promote metastasis in ER WT and MUT xenografts and an ER MUT patient derived xenograft (PDX) model. However, obASCs promote tumor growth only in ER WT xenografts.

scholarly journals Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis

2004 ◽  
Vol 24 (22) ◽  
pp. 9726-9735 ◽  
Author(s):  
Julie A. Nagle ◽  
Zhefu Ma ◽  
Maura A. Byrne ◽  
Morris F. White ◽  
Leslie M. Shaw
Keyword(s):  
Breast Cancer ◽  
Insulin Receptor ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
T Antigen ◽  
Insulin Receptor Substrate ◽  
Mammary Tumor Cells

ABSTRACT The insulin receptor substrate (IRS) proteins are adaptor molecules that integrate signals generated by receptors that are implicated in human breast cancer. We investigated the specific contribution of IRS-2 to mammary tumor progression using transgenic mice that express the polyoma virus middle T antigen (PyV-MT) in the mammary gland and IRS-2-null (IRS-2−/−) mice. PyV-MT-induced tumor initiation and growth were similar in wild-type (WT) and IRS-2−/− mice. However, the latency and incidence of metastasis were significantly decreased in the absence of IRS-2 expression. The contribution of IRS-2 to metastasis is intrinsic to the tumor cells, because IRS-2−/− mammary tumor cells did not metastasize when grown orthotopically in the mammary fat pads of WT mice. WT and IRS-2−/− tumors contained similar numbers of mitotic cells, but IRS-2−/− tumors had a higher incidence of apoptosis than did WT tumors. In vitro, IRS-2−/− mammary tumor cells were less invasive and more apoptotic in response to growth factor deprivation than their WT counterparts. In contrast, IRS-1−/− tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis.

Targeting Monoacylglycerol Lipase in Triple Negative Breast Cancer Reduced Tumor-Associated Inflammation, Tumor Growth and Tumor Colonization in the Brain

2021 ◽  
Author(s):  
Othman Benchama ◽  
Sergiy Tyukhtenko ◽  
Michael S. Malamas ◽  
Mark K. Williams ◽  
Alexandros Makriyannis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Monoacylglycerol Lipase ◽  
Breast Cancers ◽  
Novel Treatments ◽  
The Brain

Abstract While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.

scholarly journals IGF1 dependence of dietary energy balance effects on murine Met1 mammary tumor progression, epithelial-to-mesenchymal transition, and chemokine expression

2012 ◽  
Vol 20 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Nikki A Ford ◽  
Nomeli P Nunez ◽  
Valerie B Holcomb ◽  
Stephen D Hursting
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Murine Model ◽  
Epithelial To Mesenchymal Transition ◽  
Luminal Breast Cancer ◽  
Growth Factor Signaling ◽  
Mesenchymal Transition ◽  
Chemokine Expression ◽  
Mammary Tumor Growth

Luminal breast tumors with little or no estrogen receptor α expression confer poor prognosis. Using the Met1 murine model of luminal breast cancer, we characterized the IGF1-dependency of diet-induced obesity (DIO) and calorie restriction (CR) effects on tumor growth, growth factor signaling, epithelial-to-mesenchymal transition (EMT), and chemokine expression. Liver-specific IGF1-deficient (LID) and littermate control (LC) mice were administered control, DIO, or 30% CR diets for 3 months before orthotopic injection of Met1 cells. Tumors grew for 1 month and then were assessed for Akt pathway activation and mRNA expression of chemokine and EMT constituents. LID mice, regardless of diet, displayed reduced Met1 tumor growth and downregulated Akt, EMT, and chemokine pathways. CR, relative to control, reduced serum IGF1 and Met1 tumor growth in LC (but not LID) mice. DIO, relative to control, increased Met1 tumor growth and chemokine expression in LID mice, and had no effect on serum IGF1 or pAkt or cyclin D1 expression in either genotype. Thus, circulating IGF1 (in association with Akt, EMT, and chemokines) regulated Met1 tumor growth. While the anticancer effects of CR were largely IGF1-dependent, the procancer effects of DIO manifested only when circulating IGF1 levels were low. Thus, in a murine model of luminal breast cancer, IGF1 and its downstream signaling pathway, EMT, and chemokines present possible mechanistic regulatory targets. Transplanted MMTV1 Wnt1 mammary tumor growth was also reduced in LID mice, relative to LC mice, suggesting that the IGF1 effects on mammary tumor growth are not limited to Met1 tumors.

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