Early impact of social isolation and breast tumor progression in mice.
Early impact of social isolation and breast tumor progression in mice.
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DOI：
10.1016/j.bbi.2012.05.003
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发表时间：
2013-03
影响因子：
15.1
通讯作者：
Brown, Edward B.
中科院分区：
文献类型：
--
作者：
Madden, Kelley S.;Szpunar, Mercedes J.;Brown, Edward B.
来自癌症患者和癌症动物模型的证据表明，暴露于心理社会应激可以促进肿瘤生长和转移，但应激诱导的癌症发病机制的潜在途径尚未完全了解。社会隔离已被证明会促进肿瘤进展。我们使用人乳腺癌细胞系MDA-MB-231（一种高β-肾上腺素能受体（AR）表达细胞系）研究了社会隔离对成年雌性严重联合免疫缺陷（SCID）小鼠乳腺癌发病机制的影响。当在MB-231肿瘤细胞注射到乳腺脂肪垫（原位）前一周将适应组的小鼠转移到单个圈养（社会隔离）中时，与分组圈养小鼠相比，未检测到肿瘤生长或转移的变化。当社会隔离被推迟，直到肿瘤是可触及的，肿瘤生长是短暂的增加，在单圈养小鼠。为了确定交感神经系统激活是否与增加的肿瘤生长相关，在社会隔离后测量脾脏和肿瘤去甲肾上腺素（NE），连同促肿瘤巨噬细胞群体。转移至单笼后3天，荷瘤和非荷瘤小鼠的脾脏重量一过性增加，同时脾脏NE浓度降低和CD 11b +Gr-1+巨噬细胞升高。在社会隔离后第10天，在单独饲养的小鼠中未检测到脾脏CD 11b+群体或NE的变化。在肿瘤中，社会隔离增加了CD 11b +Gr-1+、CD 11b +Gr-1-和F4/80+巨噬细胞群，而肿瘤NE无变化。结果表明，心理压力，社会隔离，eliminating动态，但对巨噬细胞群体的短暂影响，可能促进肿瘤的生长。外周NE变化的短暂性表明，随着时间的推移，自我平衡机制可能会减轻社会隔离的影响。研究正在进行中，以确定社会隔离的肿瘤促进作用的神经内分泌机制，并确定增加的肿瘤巨噬细胞对肿瘤发病机制的贡献。
Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high ß-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the tumor-promoting effects of social isolation, and to determine the contributions of increased tumor macrophages to tumor pathogenesis.
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DOI：
10.1523/jneurosci.0450-11.2011
发表时间：
2011-04-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wohleb ES;Hanke ML;Corona AW;Powell ND;Stiner LM;Bailey MT;Nelson RJ;Godbout JP;Sheridan JF
通讯作者：
Sheridan JF
影响因子：
10.3
作者：
Saul, AN;Oberyszyn, TM;Dhabhar, FS
通讯作者：
Dhabhar, FS
影响因子：
3.3
作者：
Raju, B.;Haug, S. R.;Heyeraas, K. J.
通讯作者：
Heyeraas, K. J.
影响因子：
11.2
作者：
Sloan, Erica K.;Priceman, Saul J.;Cole, Steven W.
通讯作者：
Cole, Steven W.
影响因子：
2.3
作者：
REYNOLDS, P;KAPLAN, GA
通讯作者：
KAPLAN, GA