Hinterleitner Clemens, Zhou Yanjun, Tandler Claudia, Heitmann Jonas S, Kropp Korbinian N, Hinterleitner Martina, Koch André, Hartkopf Andreas D, Zender Lars, Salih Helmut R, Maurer Stefanie
Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany.
Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany.
Front Oncol. 2021 Mar 17;11:642170. doi: 10.3389/fonc.2021.642170. eCollection 2021.
Although treatment options in breast cancer have been improved significantly, predictive biomarkers for disease progression and metastasis are still lacking. Recent studies indicate that several TNF Receptor Superfamily members are involved in breast cancer cell proliferation and survival. Interestingly, () mRNA level were of prognostic relevance in breast cancer patients. In this study we provide evidence for TACI expression on platelets of breast cancer patients. The level of platelet-expressed TACI (pTACI) was significantly increased on platelets derived from breast cancer patients compared to healthy controls. Upon platelet activation, pTACI was downregulated on the platelet surface of healthy donors and breast cancer patients. Of note, inhibition of matrix metalloprotease (MMP) prevented downregulation of pTACI , indicating that proteolytic cleavage of pTACI is responsible for reduction of pTACI level. Stimulation of pTACI BAFF, BAFF 60-mer or APRIL did not influence platelet activation and function. Remarkably, pTACI was particularly regulated during tumor progression in our breast cancer cohort. TACI expression levels on platelets were correlated with clinical parameters including tumor stage, occurrence of metastasis and tumor cell proliferation (Ki67). In conclusion, our data emphasize the potential use of platelets as a liquid biomarker in breast cancer.
尽管乳腺癌的治疗选择已显著改善，但仍缺乏疾病进展和转移的预测生物标志物。最近的研究表明，几个肿瘤坏死因子受体超家族成员参与乳腺癌细胞的增殖和存活。有趣的是，（）mRNA水平在乳腺癌患者中具有预后相关性。在本研究中，我们提供了乳腺癌患者血小板上存在TACI表达的证据。与健康对照相比，乳腺癌患者来源的血小板上血小板表达的TACI（pTACI）水平显著升高。血小板激活后，健康供体和乳腺癌患者的血小板表面pTACI下调。值得注意的是，基质金属蛋白酶（MMP）的抑制可防止pTACI下调，表明pTACI的蛋白水解切割是pTACI水平降低的原因。用BAFF、BAFF 60聚体或APRIL刺激pTACI不影响血小板激活和功能。值得注意的是，在我们的乳腺癌队列中，pTACI在肿瘤进展过程中受到特别调节。血小板上的TACI表达水平与包括肿瘤分期、转移发生和肿瘤细胞增殖（Ki67）在内的临床参数相关。总之，我们的数据强调了血小板作为乳腺癌液体生物标志物的潜在用途。
