研究发现，黑色素瘤患者中 CXC 基序趋化因子 10 (CXCL10) 的上调与黑色素瘤进展相关。然而，来自宿主的内源性CXCL10在黑色素瘤生长中的作用仍不清楚。在本研究中，我们发现在皮下 B16F10 黑色素瘤肿瘤生长过程中，宿主衍生的内源性 CXCL10 产量显着增加，并且 Cxcl10-/- 小鼠中 CXCL10 的宿主消融显示体内 B16F10 黑色素瘤的血管生成和肿瘤生长均减少。 B16F10 黑色素瘤细胞中的 CXCL10 激活了一些涉及促血管生成因子产生和肿瘤生长的信号通路。 CXCL10 增加促血管生成因子的表达，例如血管内皮生长因子 (VEGF)、血小板源性生长因子 B 亚基 (PDGF-B)、成纤维细胞生长因子 2 (FGF2)、肝细胞生长因子 (HGF) 和血管生成素2 (Angpt2)，在 B16F10 黑色素瘤细胞中，导致体外人脐静脉内皮细胞的管形成和增殖增强。此外，CXCL10在体外三维细胞培养系统中直接增强B16F10黑色素瘤肿瘤的生长。总之，我们的研究结果表明，扩增的宿主来源的内源性 CXCL10 对于 B16F10 黑色素瘤血管生成和肿瘤生长至关重要。因此，CXCL10 可能代表黑色素瘤的治疗靶点。© 2024 作者。由 Informa UK Limited 出版，以 Taylor 名义进行交易

Upregulation of CXC motif chemokine 10 (CXCL10) in melanoma patients has been found to be associated with melanoma progression. However, the role of endogenous CXCL10 from the host in melanoma tumor growth remains unclear. In the present study, we found that host-derived endogenous CXCL10 production was dramatically augmented during subcutaneous B16F10 melanoma tumor growth and that host ablation of CXCL10 in Cxcl10-/- mice showed a decrease in both angiogenesis and tumor growth of B16F10 melanoma in vivo. Several signaling pathways involved in production of pro-angiogenic factors and tumor growth were activated by CXCL10 in B16F10 melanoma cells. CXCL10 increased expression of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor subunit-B (PDGF-B), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and angiopoietin 2 (Angpt2), in B16F10 melanoma cells, resulting in enhanced tube formation and proliferation of human umbilical vein endothelial cells in vitro. In addition, CXCL10 directly enhanced B16F10 melanoma tumor growth in an in vitro three-dimensional cell culture system. Together, our findings reveal that amplified host-derived endogenous CXCL10 is critical for B16F10 melanoma angiogenesis and tumor growth. Therefore, CXCL10 might represent a therapeutic target for melanoma.© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.