Inhibition of metastasis by inhibition of tumor-derived CCL5.
To determine whether tumor-derived CCL5 contributes to the metastatic potential of murine mammary carcinoma, we used the 4T1 tumor which spontaneously metastasizes and constitutively produces CCL5. Mice bearing 4T1 that expressed less CCL5 had significantly fewer lung and liver metastasis. The decrease in tumor-derived CCL5 also correlated with decreased cathepsin L, MMP-2, MMP-3, MMP-10 and MMP-17 gene expression. Thus, inhibition of tumor-derived CCL5 can impact the metastatic capability of 4T1 and may do so by modulating protease expression.
Stormes
Kerry A
KA
Department of Biology, Lafayette College, Easton, PA, USA.
Lemken
Charles A
CA
Lepre
James V
JV
Marinucci
Michelle N
MN
Kurt
Robert A
RA
D000818:Animals; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary / Q000662:veterinary; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary / Q000662:veterinary; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010447:Peptide Hydrolases / Q000096:biosynthesis
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D010447:Peptide Hydrolases