Expression of the chemokine receptor CCR6 in the Lewis lung carcinoma (LLC) cell line reduces its metastatic potential in vivo.
Chemokines and their receptors play important roles in various aspects of tumoral processes, and evidence was provided for their critical involvement in determining the metastatic destination of tumor cells. Here, we analyzed in vitro and in vivo, how CCR6 expression could alter the behavior of Lewis lung carcinoma (LLC) cells, which were shown to express low levels of the CCR6 ligand, CCL20 (LARC), both in vitro and in vivo. The expression of CCR6 significantly decreased the number of metastases in immunocompetent C57BL/6 mice, without affecting the tumor-forming ability of LLC cells. This was correlated with a decrease in clonogenicity in soft and hard agar, and with increased adhesion to type-IV collagen. These two observations made in basal conditions were enhanced when CCL20 was added to the assay medium. Thus, expression of CCR6 in tumor cells, associated with the local production of CCL20, decreased the metastatic potential of the LLC line. We propose a model, in which the expression of a chemokine receptor in tumor cells can act as a metastasis-suppressor, or a metastasis-promoting factor, according to the expression, or the absence of expression of the cognate ligand(s) in the tumor.
Sutherland
A
A
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels, Belgium.
Mirjolet
J-F
JF
Maho
A
A
Parmentier
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000517:prevention & control / Q000556:secondary*; D002448:Cell Adhesion; D049109:Cell Proliferation; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics; D002633:Chemotaxis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D002118:Calcium