葡萄膜黑色素瘤（uveal melanoma，UM）是一种常见的成人原发性眼内肿瘤，恶性程度高且易发生肝转移，一旦发生肝转移则无有效的治疗手段，是导致UM病人死亡的主要原因。所以，开发出新型靶向治疗UM尤其是靶向转移性UM的药物显得尤为重要。我们前期研究发现盘状结构域DDR1在UM细胞系与UM病人标本中高表达，且DDR1特异性配体胶原在UM病人的肝脏转移灶也大存在大量沉积，因此我们提出假设：DDR1是否通过与胶原相互作用介导UM细胞与肝脏肿瘤微环境的相互作用，促进UM细胞在肝脏中的恶性克隆增殖并发生转移。本课题在前期研究基础上，进一步通过细胞系，病人标本及体内动物实验，明确微环境来源的胶原激活DDR1后对UM恶性表型如增殖、迁移、侵袭、肿瘤干细胞及肝转移的调控作用和分子机制，拟为DDR1抑制剂7rh应用于UM肝转移治疗提供理论与实验依据。

Hepatic metastasis is the major and direct cause of death in uveal melanoma (UM) patients with no effective treatments. Mechanism exploration and improved treatments for hepatic metastatic patients with UM were urgently needed. Because discoidin domain recptor 1 (DDR1) was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of collagen, a specific type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated hypothesis that DDR1 and its ligand might bridge the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. Based on the previous research, we further confirmed the role of DDR1 in regulating the malignant phenotypes such as proliferation, migration, invasion, tumor stem cells and liver metastasis activated by microenvironment derived collagen I. Our study may provide theoretical and experimental basis for the application of DDR1 inhibitor 7rh in the treatment of liver metastases in UM.