Investigation and therapeutic application of the cancerauto-activation pathway through generation of anaphylatoxin C5a

过敏毒素C5 a受体（C5 aR）在所有检查器官的癌细胞中均有表达，且在器官中的表达率不同。几种癌细胞系也表达C5 aR。C5 a以MMP-6依赖的方式增强表达C5 aR的癌细胞在Matrigel腔室和移植的裸鼠皮肤中的侵袭。C5 a还以C5 aR依赖的方式促进癌细胞的肺转移。通过细胞膜结合的弗林蛋白酶样丝氨酸蛋白酶，癌细胞从C5产生C5 a，甚至在血浆中，增强了它们的侵袭性。抗C5 a或C5 aR的抗体和C5 aR拮抗剂可抑制C5 a对癌细胞的作用。这些结果表明存在通过C5 a生成的癌细胞自激活途径，并提示靶向C5 a-C5 aR轴或癌症蛋白酶的新癌症疗法的可用性。

Anaphylatoxin C5a receptor (C5aR) was expressed in cancer cellsfrom all organs examined and at various rates in organs. Several cancer cell lines alsoexpressed C5aR. C5a augmented C5aR-expressing cancer cell invasion in a MMP-6 dependentmanner in Matrigel chambers and in implanted nude mouse skin. C5a also enhanced cancercell lung metastasis in a C5aR-dependent manner. By cell membrane-bound furin-like serineprotease cancer cells generated C5a from C5, even it in plasma, augmenting theirinvasiveness. These C5a effects on cancer cells were inhibited by antibodies againsteither C5a or C5aR, and by a C5aR antagonist. These results indicate presence of a cancercell autoactivation pathway via C5a generation and suggest availability of a new cancertherapy targeting the C5a-C5aR axis or the cancer protease.