Kitamura Takanori, Taketo Makoto M
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cancer Res. 2007 Nov 1;67(21):10099-102. doi: 10.1158/0008-5472.CAN-07-2100.
Tumor-stromal interaction is implicated in many stages of tumor development, although it remains unclear how genetic lesions in tumor cells affect stromal cells. We have recently shown that inactivation of transforming growth factor-beta family signaling within colon cancer epithelium increases chemokine CC chemokine ligand 9 (CCL9) and promotes recruitment of the matrix metalloproteinase (MMP)-expressing stromal cells that carry CC chemokine receptor 1 (CCR1), the cognate receptor for CCL9. We have further shown that lack of CCR1 prevents the accumulation of MMP-expressing cells at the invasion front and suppresses tumor invasion. These results provide the possibility of a novel therapeutic strategy for advanced cancer--prevention of the recruitment of MMP-expressing cells by chemokine receptor antagonist.
肿瘤-基质相互作用参与肿瘤发展的多个阶段，尽管肿瘤细胞中的基因损伤如何影响基质细胞仍不清楚。我们最近发现，结肠癌上皮细胞内转化生长因子-β家族信号失活会增加趋化因子CC趋化因子配体9（CCL9），并促进携带CC趋化因子受体1（CCR1，CCL9的同源受体）的基质金属蛋白酶（MMP）表达细胞的募集。我们进一步发现，缺乏CCR1可阻止MMP表达细胞在侵袭前沿的积聚，并抑制肿瘤侵袭。这些结果为晚期癌症提供了一种新的治疗策略——通过趋化因子受体拮抗剂预防MMP表达细胞的募集。
