Liu Li-Li, Chen Shi-Lu, Huang Yu-Hua, Yang Xia, Wang Chun-Hua, He Jie-Hua, Yun Jing-Ping, Luo Rong-Zhen
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou 510060, China.
Department of Pathology, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Am J Transl Res. 2020 Mar 15;12(3):773-786. eCollection 2020.
Cancer metastasis is the major reason for cancer-related deaths, but the mechanism of cancer metastasis still unclear. Adrenomedullin (ADM), a peptide hormone, functions as a local paracrine and autocrine mediator with multiple biological activities, such as angiogenesis, cell proliferation, and anti-inflammation. However, the expression and potential function of ADM in triple-negative breast cancer (TNBC) remain unclear.
Real-time polymerase chain reaction and western blotting were performed to examine the expression of ADM in TNBC tissues and cell lines. A total of 458 TNBC tissue samples and adjacent nontumor tissue samples were detected by immunochemistry to determine the correlation between ADM expression and clinicopathological characteristics. We determined the role and mechanistic pathways of ADM in tumor metastasis in cell lines.
Our data showed that ADM expression was noticeably decreased in TNBC samples and cell lines. Low expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, low ADM expression was associated with poor prognosis and was an independent marker for TNBC. In vitro, ADM may decrease cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition.
Our findings suggest that ADM is a valuable biomarker for TNBC prognosis and an anti-metastasis candidate therapeutic target in triple-negative breast cancer.
癌症转移是癌症相关死亡的主要原因，但癌症转移的机制仍不清楚。肾上腺髓质素（ADM）是一种肽类激素，作为一种局部旁分泌和自分泌介质，具有多种生物学活性，如血管生成、细胞增殖和抗炎作用。然而，ADM在三阴性乳腺癌（TNBC）中的表达及潜在功能仍不清楚。
采用实时聚合酶链反应和蛋白质印迹法检测ADM在TNBC组织和细胞系中的表达。通过免疫组织化学检测458例TNBC组织样本和相邻非肿瘤组织样本，以确定ADM表达与临床病理特征之间的相关性。我们在细胞系中确定了ADM在肿瘤转移中的作用及作用机制途径。
我们的数据显示，ADM在TNBC样本和细胞系中的表达明显降低。低表达水平与复发和转移风险增加相关。此外，ADM低表达与预后不良相关，是TNBC的一个独立标志物。在体外，ADM可能会降低癌细胞的侵袭能力，这可能是其对癌细胞上皮-间质转化作用的结果。
我们的研究结果表明，ADM是TNBC预后的一个有价值的生物标志物，也是三阴性乳腺癌抗转移候选治疗靶点。
