Wang Yuanyuan, Schneider Stefan W, Gorzelanny Christian
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Cancers (Basel). 2023 Jun 1;15(11):3025. doi: 10.3390/cancers15113025.
Cancer metastasis is a complex process. After their intravasation into the circulation, the cancer cells are exposed to a harsh environment of physical and biochemical hazards. Whether circulating tumor cells (CTCs) survive and escape from blood flow defines their ability to metastasize. CTCs sense their environment with surface-exposed receptors. The recognition of corresponding ligands, e.g., fibrinogen, by integrins can induce intracellular signaling processes driving CTCs' survival. Other receptors, such as tissue factor (TF), enable CTCs to induce coagulation. Cancer-associated thrombosis (CAT) is adversely connected to patients' outcome. However, cancer cells have also the ability to inhibit coagulation, e.g., through expressing thrombomodulin (TM) or heparan sulfate (HS), an activator of antithrombin (AT). To that extent, individual CTCs can interact with plasma proteins, and whether these interactions are connected to metastasis or clinical symptoms such as CAT is largely unknown. In the present review, we discuss the biological and clinical relevance of cancer-cell-expressed surface molecules and their interaction with plasma proteins. We aim to encourage future research to expand our knowledge of the CTC interactome, as this may not only yield new molecular markers improving liquid-biopsy-based diagnostics but also additional targets for better cancer therapies.
癌症转移是一个复杂的过程。癌细胞进入循环系统后，会面临物理和生化危害的恶劣环境。循环肿瘤细胞（CTC）能否存活并从血流中逃逸决定了它们的转移能力。CTC通过表面暴露的受体感知其环境。整合素对相应配体（如纤维蛋白原）的识别可诱导驱动CTC存活的细胞内信号传导过程。其他受体，如组织因子（TF），可使CTC诱导凝血。癌症相关血栓形成（CAT）与患者的预后呈负相关。然而，癌细胞也有抑制凝血的能力，例如通过表达血栓调节蛋白（TM）或硫酸乙酰肝素（HS），后者是抗凝血酶（AT）的激活剂。在这种程度上，单个CTC可与血浆蛋白相互作用，而这些相互作用是否与转移或诸如CAT等临床症状相关，在很大程度上尚不清楚。在本综述中，我们讨论了癌细胞表达的表面分子的生物学和临床相关性及其与血浆蛋白的相互作用。我们旨在鼓励未来的研究扩展我们对CTC相互作用组的认识，因为这不仅可能产生改善基于液体活检的诊断的新分子标志物，还可能产生更好的癌症治疗的额外靶点。
