Keeping out the bad guys: gateway to cellular target therapy.
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.
Kitamura
Takanori
T
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Taketo
Makoto M
MM
D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D002450:Cell Communication; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000502:physiology; D019742:Chemokines, CC / Q000502:physiology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology
D039481:CD11b Antigen; C095218:Ccl9 protein, mouse; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D061965:Matrix Metalloproteinase Inhibitors; D054389:Receptors, CCR1; D020782:Matrix Metalloproteinases