Abstract 1011: Metformin inhibits angiogenesis, local and metastatic growth of triple-negative breast cancer by targeting two classes of adipose tissue progenitors

2014 ◽  
Author(s):  
Stefania Orecchioni ◽  
Giuliana Gregato ◽  
Francesca Reggiani ◽  
Patrizia Mancuso ◽  
Angelica Calleri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Growth

scholarly journals Interface between obesity with dysfunctional metabolism and inflammation, and the triple-negative breast cancer in African American women

2021 ◽  
pp. 602-616
Author(s):  
Katarzyna Rygiel
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
African American ◽  
Aggressive Behavior ◽  
African American Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Networks ◽  
Biological Variables ◽  
Inflammatory Processes

Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant “obese” tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the “obese” TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, “flexible” metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women.

scholarly journals Active behavior of triple-negative breast cancer with adipose tissue invasion: a single center and retrospective review

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junzo Yamaguchi ◽  
Hiroki Moriuchi ◽  
Takashi Ueda ◽  
Yujo Kawashita ◽  
Takanori Hazeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Systemic Disease ◽  
Hazard Ratio ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Tissue Invasion

Abstract Background Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR−/HER2-). Methods A total of 735 patients with early-stage invasive BC (1999–2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model. Results Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). Conclusions Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.

scholarly journals Active Behavior of Triple-negative Breast Cancer With Adipose Tissue Invasion: A Single Center and Retrospective Review

2020 ◽  
Author(s):  
Junzo Yamaguchi ◽  
Hiroki Moriuchi ◽  
Takashi Ueda ◽  
Yujo Kawashita ◽  
Takanori Hazeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Systemic Disease ◽  
Hazard Ratio ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Tissue Invasion

Abstract Background: Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). Methods: A total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model.Results: Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). Conclusions: Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.

scholarly journals Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture

2020 ◽  
Vol 21 (17) ◽  
pp. 6439
Author(s):  
Emmanuel C. Asante ◽  
Nikitha K. Pallegar ◽  
Alica J. Hoffmann ◽  
Alicia M. Viloria-Petit ◽  
Sherri L. Christian
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Obese Mice ◽  
Breast Cancer Patients ◽  
Mesenchymal To Epithelial Transition

Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis.

scholarly journals Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer

2019 ◽  
Vol 216 (6) ◽  
pp. 1345-1358 ◽  
Author(s):  
Payal Tiwari ◽  
Ariane Blank ◽  
Chang Cui ◽  
Kelly Q. Schoenfelt ◽  
Guolin Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Formation ◽  
Dependent Manner ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
Adipose Tissue Macrophages ◽  
Macrophage Accumulation

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)–dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.

scholarly journals Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Triple Negative Breast Cancer Xenografts

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89595 ◽  
Author(s):  
Brian G. Rowan ◽  
Jeffrey M. Gimble ◽  
Mei Sheng ◽  
Muralidharan Anbalagan ◽  
Ryan K. Jones ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Human Adipose Tissue ◽  
Early Metastasis ◽  
Stromal Stem Cells ◽  
Breast Cancer Xenografts

scholarly journals Metabolically activated macrophages in mammary adipose tissue link obesity to triple-negative breast cancer

2018 ◽  
Author(s):  
Payal Tiwari ◽  
Ariane Blank ◽  
Chang Cui ◽  
Kelly Q. Schoenfelt ◽  
Guolin Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Formation ◽  
List Type ◽  
Dependent Manner ◽  
Macrophage Phenotype ◽  
Adipose Tissue Macrophages

SUMMARYObesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Macrophages, which accumulate in adipose tissue and are activated during obesity, are an attractive mechanistic link. Here, we show that, during obesity, murine and human mammary adipose tissue macrophages adopt a pro-inflammatory, metabolically- activated (MMe) macrophage phenotype that promotes TNBC stem-like markers and functions, including increased tumorsphere growthin vitroand tumor-initiating potentialin vivo. We demonstrate that MMe macrophages release cytokines in an NADPH oxidase 2 (NOX2)-dependent manner that signal through glycoprotein 130 (GP130) on TNBC cells to promote their stem-like properties. Accordingly, deletingNox2in myeloid cells or depleting GP130 in TNBC cells attenuates the ability of obesity to drive TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue during obesity as a mechanism for promoting TNBC stemness and tumorigenesis.HIGHLIGHTS⁘Obesity promotes TNBC tumor formation and stemness.⁘Mammary adipose tissue macrophages are metabolically activated (MMe) in obese mice and humans.⁘MMe macrophages in mammary adipose tissue contribute to obesity-induced stemness.⁘MMe macrophages promote TNBC stemness through GP130 signaling.

scholarly journals Active Behavior of Triple-Negative Breast Cancer With Adipose Tissue Invasion: A Single Center and Retrospective Review

2021 ◽  
Author(s):  
junzo yamaguchi ◽  
Hiroki Moriuchi ◽  
Takashi Ueda ◽  
Yujo Kawashita ◽  
Takanori Hazeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Systemic Disease ◽  
Hazard Ratio ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Tissue Invasion

Abstract BackgroundInteractions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). MethodsA total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model.ResultsPatients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). ConclusionsAdipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.

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