Ließem Anne, Leimer Uwe, Germann Günter K, Köllensperger Eva
Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine - ETHIANUM, Heidelberg, 69115, Germany.
Breast Cancer (Dove Med Press). 2025 Jan 25;17:79-102. doi: 10.2147/BCTT.S491277. eCollection 2025.
Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute to breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of their involvement are not yet completely understood.
In this project, varying concentrations of recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, and Resistin) were used to study their effects on four selected breast cancer cell lines (EVSA-T, MCF-7, MDA-MB-231, and SK-Br-3). Over a five-day proliferation phase, linear growth was assessed by calculating doubling times and malignancy-associated changes in gene and protein expression were identified using quantitative TaqMan real-time PCR and multiplex protein analysis. Migration and invasion behaviors were quantified using specialized Boyden chamber assays.
We found significant, adipokine-mediated genetic and proteomic alterations, with PCR showing an up to 6-fold increase of numerous malignancy-associated genes after adipokine-supplementation. Adipokines further altered protein secretion, such as raising the concentrations of different tumor-associated proteins up to 13-fold. Effects on proliferation varied, however, with most approaches showing significant enhancement in growth kinetics. A concentration-dependent increase in migration and invasion was generally observed, with no significant reductions in any approaches.
We could show a robust promoting effect of several adipokines on different breast cancer cells in vitro. Understanding the interaction between adipose tissue and breast cancer cells opens potential avenues for innovative breast cancer prevention and therapy strategies. Our findings indicate that antibodies against specific adipokines could become a beneficial component of clinical breast cancer treatment in the future.
脂肪因子是由脂肪组织分泌的生物活性肽，似乎在乳腺癌的发生和发展中起作用。虽然大量研究表明它们在促进肿瘤生长方面的作用，但其确切的参与机制尚未完全了解。
在本项目中，使用不同浓度的重组人脂肪因子（瘦素、脂质运载蛋白-2、纤溶酶原激活物抑制剂-1和抵抗素）来研究它们对四种选定的乳腺癌细胞系（EVSA-T、MCF-7、MDA-MB-231和SK-Br-3）的影响。在为期五天的增殖阶段，通过计算倍增时间评估线性生长，并使用定量TaqMan实时PCR和多重蛋白质分析确定基因和蛋白质表达中与恶性肿瘤相关的变化。使用专门的博伊登室测定法对迁移和侵袭行为进行定量。
我们发现了显著的、脂肪因子介导的基因和蛋白质组学改变，PCR显示在添加脂肪因子后，许多与恶性肿瘤相关的基因增加了多达6倍。脂肪因子进一步改变了蛋白质分泌，例如将不同肿瘤相关蛋白的浓度提高了多达13倍。然而，对增殖的影响各不相同，大多数方法显示生长动力学有显著增强。一般观察到迁移和侵袭呈浓度依赖性增加，在任何方法中均未观察到显著降低。
我们可以证明几种脂肪因子在体外对不同乳腺癌细胞具有强大的促进作用。了解脂肪组织与乳腺癌细胞之间的相互作用为创新的乳腺癌预防和治疗策略开辟了潜在途径。我们的研究结果表明，针对特定脂肪因子的抗体未来可能成为临床乳腺癌治疗的有益组成部分。
