Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE, USA.
Eppley Institute, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE, USA.
Pharmacol Ther. 2017 Nov;179:158-170. doi: 10.1016/j.pharmthera.2017.05.012. Epub 2017 May 23.
Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression. This receptor, in conjunction with its primary chemokine ligand CXCL12, promotes pancreatic cancer development, invasion, and metastasis through the management of the tumor microenvironment via complex crosstalk with other pathways. Thus, CXCR4 likely contributes to the poor prognoses observed in patients afflicted with this malignancy. Recent exploration of combination therapies with CXCR4 antagonists have demonstrated improved outcomes, and abolishing the contribution of this pathway may prove crucial to effectively treat pancreatic cancer at both the primary tumor and metastases.
趋化因子网络调节着各种细胞、生理和免疫过程。这些正常功能可能被癌细胞利用，通过促进生长、增殖和转移，为异常细胞创造更适宜的微环境。在胰腺癌中尤其如此，趋化因子信号是支持肿瘤微环境形成以及癌细胞与周围基质细胞之间信号传递的重要组成部分。尽管在不同的癌症类型中表达模式存在差异，但趋化因子受体 CXCR4 几乎与每种主要恶性肿瘤都有关联，并在胰腺癌的发生和发展中发挥重要作用。该受体与其主要趋化因子配体 CXCL12 一起，通过与其他途径的复杂串扰来管理肿瘤微环境，从而促进胰腺癌的发展、侵袭和转移。因此，CXCR4 可能导致患有这种恶性肿瘤的患者预后不良。最近对 CXCR4 拮抗剂联合治疗的探索表明，改善了治疗效果，而消除该途径的作用可能对有效治疗原发性肿瘤和转移灶的胰腺癌至关重要。
