在发表的文章中Breast Cancer Research，里昂癌症研究中心的查尔斯·杜蒙特（Charles Dumontet）的团队表明，围绕乳腺癌的脂肪组织增加了对trastuzumab（或赫斯蒂汀）的抵抗力，这是一种针对癌基因HER-2的治疗性单克隆抗体。脂肪组织对癌症的犯罪继续增加，但一开始似乎是如此无辜！

脂肪组织：在看似温顺的外部，是高度活跃的组织

乍一看，脂肪组织似乎是一种相当单调的组织，主要由脂肪细胞，脂肪储存细胞组成。这些球状细胞包含一个大型脂质液泡（由甘油三酸酯组成）。

Their main function is to maintain an energy balance by storing excess fat and releasing it when needed in the form of fatty acids. However, an adipocyte is not only a passive “fat reservoir”. We now know it has other very active functions: it produces and secretes many biomolecules such as hormones, growth factors and proinflammatory cytokines, a group of molecules named adipokines.

脂肪组织还包含其他比脂肪细胞且在组织切片上几乎看不见的细胞。在其他细胞中，有成纤维细胞，内皮细胞和巨噬细胞以及脂肪细胞祖细胞（脂肪衍生的干细胞，前脂肪细胞），这些祖细胞支持脂肪组织的更新。

Histological examination of normal mammary adipose tissue after Hematoxylin-Eosin (HE) staining (original magnification X 400). Note that mature white adipocytes have a single lipid droplet (in white), which essentially occupies the fat cell volume surrounded by a reduced rim of cytoplasm. © Ghislaine Escourrou

Adipose tissue and breast cancer: A dangerous dynamic duo

In the breast, adipose tissue is particularly abundant and surrounds the mammary glands. Thus, when breast cancer becomes invasive, it comes into direct contact with fatty tissue. Recently, numerous studies have shown that adipocytes and their progenitors promote breast cancer aggressiveness by stimulating proliferation and, especially, invasion by secreting proteases, pro-inflammatory cytokines and by modulating cancer cell metabolism.

在肥胖中，不仅规模和数量，而且脂肪细胞的分泌物也受到深远的影响。肥胖的乳腺癌患者在诊断时表现出更多的攻击性肿瘤，疾病进展为死亡率更高。因此，研究脂肪细胞对疾病进展的影响对医学具有主要兴趣，尤其是对于肥胖患者的治疗。

当前的论文对脂肪组织可能在抗癌治疗中起作用的作用提出了令人信服的假设，从而保护了肿瘤细胞免受其毒性作用的影响。这可能解释了尽管据称有足够的治疗计划，但肥胖乳腺癌患者中观察到的存活率降低。

In breast cancer, early local tumor invasion results in immediate proximity of cancer cells to adipose tissue. Histological examination of an invasive breast tumor after H&E staining (original magnification X 200). Arrows indicate the tumor. Note that at the invasive front, tumor and adipose tissue are in contact (indicated by stars). © Ghislaine Escourrou

曲妥珠单抗, a targeted weapon thwarted by fat cells

近年来，已经努力开发有针对性的癌症治疗疗法。这种类型的治疗特异性靶向异常，通过特异性消除或阻断肿瘤细胞的生长，而不是损害正常细胞和癌细胞的传统疗法，从而导致癌症的生长和扩散。

曲妥珠单抗(Herceptin ™) is part of this family and has shown extraordinary results in breast cancer treatment, when administered alone or in combination with chemotherapy. It is an antibody directed against HER2 receptor, which is over-expressed by breast cancer cells in approximately 20% of patients.

Despite the remarkable efficacy of this drug, some patients are resistant to this treatment either directly from the first administration, or after some time of exposure to the drug. Now, understanding the underlying mechanisms inducing this resistance is essential to further improve the efficacy of this treatment.

在这项发表的作品中Breast Cancer Research, Charles Dumontet’s team shows that fat cells decrease trastuzumab effectiveness using a variety of experimental approaches including mice models. Through secretion of soluble factors (whose precise nature remains to be identified), fat cells activate survival mechanisms in recipient tumor cells diminishing the effect of the drug.

这项研究在许多方面都是非常原始的。一方面，它首次表明脂肪细胞可能对靶向疗法的功效产生负面影响。肥胖与曲妥珠单抗的抗性之间的联系仍然受到探索，但本文凸显了临床研究的必要性来澄清这一点。

On the other hand, this work strongly suggests that the survival mechanisms activated in tumor cells by surrounding adipose tissue could also counteract the effects of other types of anti-cancer therapies, such as chemotherapy. This sheds new light on the role of fat cells in breast cancer progression and could contribute to the development of new more effective therapies, especially for the treatment of obese cancer patients.