Libby Emily Falk, Frost Andra R, Demark-Wahnefried Wendy, Hurst Douglas R
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
J Mol Med (Berl). 2014 Oct;92(10):1015-23. doi: 10.1007/s00109-014-1179-5. Epub 2014 Jun 7.
Adipokines within the tumor microenvironment may play important roles in regulating the early steps of breast cancer metastasis. Adiponectin (AdipoQ) is the most abundant adipokine and exists in multiple forms: full-length multimers (fAd) and a cleaved, globular isoform (gAd). While these isoforms are observed as having distinct biological properties, nearly all investigation into AdipoQ in breast cancer has focused on the antitumor roles of fAd, while mostly ignoring gAd. However, evidence from other disease settings suggests that gAd is linked to processes known to promote metastasis. Here, we discuss key areas in which knowledge about AdipoQ in breast cancer is lacking, expressly focusing on data suggesting that gAd is elevated in the microenvironment and may act directly on invasive breast cancer cells to support their initial metastatic progression. We discuss autophagy as a potential mechanism of action for this effect. Overall, given that AdipoQ and AdipoQ receptor agonists have been proposed as therapeutic strategies, it is necessary to better understand the various functions of these regulatory molecules in metastatic breast cancer. Doing so will help ensure the most effective approaches to treating this disease, for which there remain no curative options.
肿瘤微环境中的脂肪因子可能在调节乳腺癌转移的早期步骤中发挥重要作用。脂联素（AdipoQ）是最丰富的脂肪因子，以多种形式存在：全长多聚体（fAd）和一种裂解的球状异构体（gAd）。虽然这些异构体具有不同的生物学特性，但几乎所有关于乳腺癌中AdipoQ的研究都集中在fAd的抗肿瘤作用上，而大多忽略了gAd。然而，来自其他疾病背景的证据表明，gAd与已知促进转移的过程有关。在这里，我们讨论了乳腺癌中AdipoQ相关知识缺乏的关键领域，特别关注那些表明gAd在微环境中升高且可能直接作用于侵袭性乳腺癌细胞以支持其初始转移进展的数据。我们讨论自噬作为这种效应的潜在作用机制。总体而言，鉴于AdipoQ和AdipoQ受体激动剂已被提议作为治疗策略，有必要更好地了解这些调节分子在转移性乳腺癌中的各种功能。这样做将有助于确保采用最有效的方法来治疗这种尚无治愈选择的疾病。
