Gupta Gaorav P, Nguyen Don X, Chiang Anne C, Bos Paula D, Kim Juliet Y, Nadal Cristina, Gomis Roger R, Manova-Todorova Katia, Massagué Joan
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature. 2007 Apr 12;446(7137):765-70. doi: 10.1038/nature05760.
Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.
转移涉及众多生物学功能，这些功能共同使原发部位的癌细胞得以扩散并占据远处器官。通过遗传学和药理学方法，我们发现，当表皮生长因子受体配体埃皮瑞利素、环氧化酶COX2以及基质金属蛋白酶1和2在人乳腺癌细胞中表达时，它们共同促进新肿瘤血管的形成、肿瘤细胞释放进入循环系统，以及循环肿瘤细胞突破肺毛细血管以形成肺转移。这些发现揭示了侵袭性原发性致瘤功能如何在机制上与更高的肺转移潜能相关联，以及这些生物学活性如何通过特定药物组合进行治疗靶向。
