Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice.
Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice.
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DOI：
10.1186/bcr2927
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发表时间：
2011-08-11
期刊：
影响因子：
--
通讯作者：
Yoon Park JH
中科院分区：
文献类型：
--
作者：
Kim EJ;Choi MR;Park H;Kim M;Hong JE;Lee JY;Chun HS;Lee KW;Yoon Park JH
众所周知，高脂肪饮食(HFD)会导致肥胖，并与乳腺癌的进展和转移有关。因为肥胖与乳腺癌的进展有关，所以在没有肥胖的情况下，确定饮食脂肪本身是否刺激乳腺癌的进展是很重要的。这项研究调查了HFD是否增加了肥胖抵抗BALB/c小鼠的乳腺癌生长和转移以及死亡率。4周龄雌性BALB/c小鼠饲喂高脂饲料(60%千卡脂肪)或对照饲料(镉，10千卡脂肪)16周。随后，将4T1乳腺癌细胞注射到连续喂养的小鼠的腹股沟乳房脂肪垫中。免疫组织化学、免疫印迹和酶联免疫吸附试验分析细胞周期进程、肿瘤组织中的血管生成和免疫细胞、肺组织中的蛋白水解酶和黏附分子以及血清细胞因子水平。体外研究还评估了细胞因子对4T1细胞活力、迁移和黏附的影响。HFD组的脾和性腺脂肪垫重量、肿瘤重量、肺和肝脏肿瘤结节的数量和体积以及肿瘤相关死亡率均增加，但能量摄入量和体重仅略有增加。喂饲HF可增加脂肪组织中巨噬细胞的浸润，增加脂肪组织中脂质空泡的数量，增加肿瘤组织中细胞周期蛋白依赖性激酶(CDK)2、细胞周期蛋白D1、细胞周期蛋白A、Ki67、CD31、CD45和CD68的表达，增加血清补体片段5a(C5a)、白细胞介素16(IL-16)、巨噬细胞集落刺激因子(M-CSF)、可溶性细胞间黏附分子(SICAM)-1、金属蛋白酶组织抑制物(TIMP)-1、瘦素和髓样细胞(TREM)-1表达的触发受体的水平。HFD组肺组织尿激酶型纤溶酶原激活物、ICAM-1、血管细胞黏附分子-1蛋白水平升高，纤溶酶原激活物抑制物-1蛋白水平降低。4T1细胞体外实验显示，sICAM-1可增加细胞活力；TREM-1、TIMP-1、M-CSF和sICAM-1可促进细胞迁移；C5a、sICAM-1、IL-16、M-CSF、TIMP-1和TREM-1可增加黏附。饮食脂肪增加了乳腺肿瘤的生长和转移，从而增加了肥胖抵抗小鼠的死亡率。
High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice. The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion. Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion. Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice.
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影响因子：
2.9
作者：
McEligot, Archana Jaiswal;Largent, Joan;Anton-Culver, Hoda
通讯作者：
Anton-Culver, Hoda
影响因子：
4.2
作者：
Kim, Eun Ji;Shin, Minjeong;Park, Jung Han Yoon
通讯作者：
Park, Jung Han Yoon
影响因子：
5.6
作者：
Kwon, Gyoo Taik;Cho, Han Jin;Park, Jung Han Yoon
通讯作者：
Park, Jung Han Yoon
DOI：
10.1073/pnas.0809516106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Ford, Caroline E.;Ekstrom, Elin J.;Andersson, Tommy
通讯作者：
Andersson, Tommy
影响因子：
11.2
作者：
Banka, CL;Lund, CV;Eliceiri, BP
通讯作者：
Eliceiri, BP