Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth

2011 ◽  
Vol 301 (3) ◽  
pp. E504-E510 ◽  
Author(s):  
Pernille Hojman ◽  
Christine Dethlefsen ◽  
Claus Brandt ◽  
Jakob Hansen ◽  
Line Pedersen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Mammary Cancer ◽  
Exercise Bout ◽  
Cancer Cell Proliferation ◽  
Caspase Activity ◽  
Humoral Factors ◽  
Mammary Cancer Cell ◽  
Exercise Induced ◽  
Mcf 7

Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25–30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

scholarly journals Estrogen-Like Properties of Fluorotelomer Alcohols as Revealed by MCF-7 Breast Cancer Cell Proliferation

2006 ◽  
Vol 114 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Marleen Maras ◽  
Caroline Vanparys ◽  
Frederik Muylle ◽  
Johan Robbens ◽  
Urs Berger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Fluorotelomer Alcohols ◽  
Mcf 7

scholarly journals Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation

Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4218-4232 ◽  
Author(s):  
Chikayo Iwaya ◽  
Takashi Nomiyama ◽  
Shiho Komatsu ◽  
Takako Kawanami ◽  
Yoko Tsutsumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Abstract Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

Aberrant microRNA Expression in Radiation-Induced Rat Mammary Cancer: The Potential Role of miR-194 Overexpression in Cancer Cell Proliferation

2012 ◽  
Vol 179 (2) ◽  
pp. 151 ◽  
Author(s):  
Daisuke Iizuka ◽  
Tatsuhiko Imaoka ◽  
Mayumi Nishimura ◽  
Hidehiko Kawai ◽  
Fumio Suzuki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Mammary Cancer ◽  
Potential Role ◽  
Microrna Expression ◽  
Cancer Cell Proliferation ◽  
Radiation Induced

scholarly journals Radiation-Triggered NF-κB Activation is Responsible for the Angiogenic Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and Growth

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S9592 ◽  
Author(s):  
Hui Yu ◽  
Sumathy Mohan ◽  
Mohan Natarajan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Radiation Exposure ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Mcf 7

Tumors require blood supply to survive, grow, and metastasize. This involves the process of angiogenesis signaling for new blood vessel growth into a growing tumor mass. Understanding the mechanism of the angiogenic signaling pathway and neovascularization for breast cancer cell proliferation and growth would help to develop molecular interventions and achieve disease free survival. Our hypothesis is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic signaling pathway in the neighboring endothelial cells resulting in neovascularization for breast cancer cell growth. The angiogenic signaling pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of a transcriptional regulator NF-κB, which in turn is triggered by therapeutic doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were exposed to Cesium-137 (137Cs) γ rays to a total dose of 2 Gy at a dose rate of 1.03 Gy/min. The results of mobility shift assay showed that radiation at clinical doses (2 Gy) could induce NF-κB DNA-binding activity. Then, we examined the communication of angiogenic signals from irradiated MCF-7 cells to vascular endothelial cells. At the protein level, the western blot showed induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2 Gy. Inhibition of NF-κB activation attenuated VEGF and FGF-2 levels. These factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra cellular medium were both increased, after 2 Gy exposures. We also observed corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro tube formation assays provided evidence that irradiated MCF-7 cells transmit signals to potentiate cultured non-irradiated endothelial cells to form tube networks, which is the hallmark of neovascularization. Inhibition of NF-κB activation attenuated irradiated MCF-7-induced tube network formation. The data provide evidence that the radiation exposure is responsible for tumor growth and maintenance by inducing an angiogenic signaling pathway through activation of NF-κB.

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