Deficiency of myeloid discoidin domain receptor 2 aggravates melanoma lung and bone metastasis.

IF 3 3区 医学 Q2 ONCOLOGY Investigational New Drugs Pub Date : 2024-12-26 DOI:10.1007/s10637-024-01496-2
Yue Sun, Liangliang Wei, Hao Liu, Gaoyang Zong, Zhihao Xia, Xiangyang Li, Zhanhai Yin, Dageng Huang, Yan Zhang
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Abstract

Melanoma, one of the most prevalent cancers worldwide, frequently metastasizes to the lung and bones. Tumor-associated macrophages play essential roles in melanoma metastasis but the underlying mechanism remains obscure. We previously demonstrated that specific knockout of Ddr2, a receptor tyrosine kinase, exacerbates systemic inflammation via modulating macrophage repolarization. To investigate whether myeloid Ddr2 regulates melanoma growth and metastasis, we injected B16BL6 melanoma cells into Ddr2LysM (cKO) mice via subcutaneous neck, tail vein, and left ventricle, respectively. We found that the growth of melanoma cells in cKO mice was significantly retarded, as demonstrated by the subcutaneous transplantation tumor model. Unexpectedly, the melanoma metastasis to the lung or bone was significantly stimulated in cKO mice, indicating the complicated role of Ddr2 in macrophages in melanoma development. Furthermore, Ddr2 in macrophages regulated the migration of B16BL6 cells in the co-culture system. Bioinformatics analysis showed that Ddr2 expression correlates with improved prognostic outcomes in melanoma, and high expression of Ddr2 is protective in melanoma metastasis. Our results enrich the current knowledge of Ddr2 in tumor biology and indicate that more consideration should be taken when applying Ddr2 inhibition as a melanoma treatment strategy.

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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
期刊最新文献
A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer. Clinical features, treatment, and outcomes of nivolumab induced psoriasis. Deficiency of myeloid discoidin domain receptor 2 aggravates melanoma lung and bone metastasis. 5-Fluorouracil-methotrexate conjugate enhances the efficacy of 5-fluorouracil in colorectal cancer therapy. Efficacy and safety of the combination of envafolimab and lenvatinib in unresectable hepatocellular carcinoma: a single-arm, multicentre, exploratory phase II clinical study.
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