化学趋化因子基质细胞来源因子1（SDF-1）/CXCL12通过结合其受体CXC-4趋化因子受体（CXCR4）和CXC-7趋化因子受体（CXCR7）发挥作用。CXCL12与其受体的结合导致下游信号传导，从而导致肿瘤细胞的存活、增殖和迁移。与正常细胞相比，CXCL12和CXCR4在乳腺癌（BC）和胶质母细胞瘤（GBM）中高表达。该趋化因子轴的高表达与治疗耐药性、分级、肿瘤扩散和预后较差呈正相关。他莫昔芬（TMX）是一种选择性雌激素受体调节剂（SERM），可以抑制肿瘤细胞分泌的生长和血管生成因子等雌激素调控基因的表达。此外，TMX还作用于多种蛋白质，如蛋白激酶C（PKC）、磷脂酶C（PLC）、糖蛋白P（PgP）、磷酸肌醇-3-激酶（PI3K）和离子通道。该药物显示了对BC和GBM细胞的有希望的抗肿瘤活性。在本综述中，我们讨论了CXCL12-CXCR4-CXCR7趋化因子轴在BC和GBM肿瘤生物学中的作用，并提出了TMX作为这些肿瘤中该轴的潜在调节剂。TMX在BC中调节CXCL12-CXCR4-CXCR7轴的作用已被研究，但在GBM中尚无相关研究。我们提出，研究在接受TMX治疗的GBM细胞/患者中的该轴可能对这些患者有益。TMX抑制了这些肿瘤中重要的信号通路，而该趋化因子轴的激活与治疗耐药性增加相关。版权所有 © 2023 Elsevier Ltd. 保留所有权利。

The chemokine stromal cell-derived-factor 1 (SDF)-1/CXCL12 acts by binding to its receptors, the CXC-4 chemokine receptor (CXCR4) and the CXC-7 chemokine receptor (CXCR7). The binding of CXCL12 to its receptors results in downstream signaling that leads to cell survival, proliferation and migration of tumor cells. CXCL12 and CXCR4 are highly expressed in breast cancer (BC) and glioblastoma (GBM) compared to normal cells. High expression of this chemokine axis correlates with increased therapy resistance and grade, tumor spread and poorer prognosis in these tumors. Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) that inhibits the expression of estrogen-regulated genes, including growth and angiogenic factors secreted by tumor cells. Additionally, TMX targets several proteins, such as protein kinase C (PKC), phospholipase C (PLC), P-glycoprotein (PgP), phosphatidylinositol-3-kinase (PI3K) and ion channels. This drug showed promising antitumor activity against both BC and GBM cells. In this review, we discuss the role of the CXCL12-CXCR4-CXCR7 chemokine axis in BC and GBM tumor biology and propose TMX as a potential modulator of this axis in these tumors. TMX modulates the CXCL12-CXCR4-CXCR7 axis in BC, however, there are no studies on this in GBM. We propose that studying this axis in GBM cells/patients treated with TMX might be beneficial for these patients. TMX inhibits important signaling pathways in these tumors and the activation of this chemokine axis is associated with increased therapy resistance.Copyright © 2023 Elsevier Ltd. All rights reserved.