There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemokine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell membranes of CXCR4 has been shown to be associated with the development of different kinds of histological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors, or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and the activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs, conferring greater capacity for locoregional aggressiveness, the epithelial–mesenchymal transition (EMT), and the appearance of metastases. Therefore, it has been hypothesized as to how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets.
影响细胞生长并与癌症发展相关的分子机制已有多种明确阐述。趋化因子作为关键要素，不仅参与局部生长调控，还影响血管生成、肿瘤扩散及转移性疾病。其中，C-X-C基序趋化因子配体12（CXCL12）及其特异性受体C-X-C基序趋化因子受体4（CXCR4）已得到广泛研究。CXCR4在细胞膜上的过表达已被证实与多种组织学恶性肿瘤的发展相关，包括腺癌、表皮样癌、间叶性肿瘤及神经内分泌肿瘤（NENs）。在胃肠胰（GEP）和支气管肺（BP）神经内分泌肿瘤中，CXCL12与CXCR4的分子突触连接可介导G蛋白相互作用，激活多种细胞内信号通路，从而增强肿瘤的局部侵袭能力、促进上皮-间质转化（EMT）及转移灶形成。基于此，针对该受体的靶向工具设计已成为研究热点。本综述旨在系统阐述当前关于CXCR4与神经内分泌肿瘤关系的认知，并重点探讨其在诊断与治疗领域的分子靶点价值。
CXCR4: From Signaling to Clinical Applications in Neuroendocrine Neoplasms
肿瘤(癌症)患者之家