科学家阐明肥胖和女性乳腺癌发病风险的关联

  众所周知，肥胖是一种乳腺癌的风险因子，但研究者们并不清楚肥胖和乳腺癌的具体关联，近日刊登在国际杂志Science Translational Medicine上的一篇研究论文中，来自塔夫斯大学等处的科学家们就揭开了肥胖引发乳腺组织结构发生改变的原因，这或许是促进乳腺细胞癌变的机制，该研究对于后期开发新型的乳腺癌诊断及治疗策略提供了一定帮助。
  研究者Kuperwasser在文章中写道，肥胖在因乳腺癌死亡的女子中占到了五分之一，但不幸的是治疗乳腺癌肥胖女性的特异性非常有限，隐藏在肥胖-乳腺癌之间关联背后的分子机制让科学家们十分头疼，尽管有些研究者提出肥胖或许会引发患者机体激素或炎症出现相关性的差异。
  这项研究中，研究者对人类和小鼠的乳腺脂肪组织进行观察对比研究，结果发现，相比正常个体而言，肥胖个体机体中的纤维网状结构往往会将脂肪细胞固定起来；而研究者好奇的是是否肥胖相关的遗传特性扮演了主要的角色，随后研究者对比了遗传性肥胖和后期喂养肥胖的小鼠机体的乳腺组织，结果显示，不管小鼠是怎么变肥胖的，它们的乳腺脂肪组织都是比较僵硬的；这样研究者就排除了常见炎性分子的可能性了，他们指出，这或许是因为僵硬结构本身引发的乳腺癌。
  为了验证他们的假设，随后研究者将肥胖相关的组织样本的癌变前期的乳腺细胞暴露于僵硬的纤维网状结构中，结果显示，相比非肥胖相关的组织而言，生长在这样环境中的细胞更易于完全癌变。随后研究者表示，是否体重降低会降低乳腺脂肪组织的僵硬程度？进一步研究后他们发现，体重降低或可潜在逆转组织的僵硬程度。
  肥胖相关的乳腺癌的比率随着肥胖率的增加会相应地增加，而当前减肥被认为是乳腺癌肥胖个体治疗的一种推荐策略；服用二甲双胍的肥胖女性或患乳腺癌的风险较低，基于此糖尿病药物在临床试验中往往被用于治疗肥胖相关的乳腺癌。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis
Science Translational Medicine    DOI: 10.1126/scitranslmed.3010467 
Arendt LM1, Kuperwasser C2.
he findings, based on research with tissue from mice and humans, emphasize the need to encourage a healthy weight in women who have breast cancer and in general. The results may also have implications for breast cancer detection and breast reconstruction surgeries, the researchers reported in the Aug. 19 issue of Science Translational Medicine.
The authors of an editorial accompanying the paper said the findings could be key to solving the puzzle of how obesity leads to breast cancer or worsens outcomes for women with the disease. This kind of information could open the way to treatments that target those pathways, according to Lisa Arendt, a research assistant professor, and Charlotte Kuperwasser, an associate professor, at Tufts University in Boston.
"Unfortunately, therapeutics specific for obese women with breast cancer are limited," Arendt and Kuperwasser wrote. They said that obesity accounts for as much as one-fifth of all cancer deaths among women.
The processes underlying the obesity-breast cancer link had left specialists stumped, although some had proposed obesity-related differences in hormones or inflammation. But obesity-related stiffening of breast tissues was not high on the list.
In the new work, Cornell University doctoral student Bo Ri Seo and colleagues looked at breast fat tissue in humans and mice. They found that in obesity, the web-like network of fibers holding fat cells in place is more rigid than normal.