Role of the autocrine chemokines MIP-1alpha and MIP-1beta in the metastatic behavior of murine T cell lymphoma.
The ESb-MP T-cell line is a highly malignant murine lymphoma, which preferentially metastasizes toward the kidney. This could be a result of the local production of monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T expressed and secreted (RANTES), which are chemotactic for ESb-MP cells. Here, we demonstrate that ESb-MP cells are already responsive to the chemotactic activity of macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta from 1 ng/ml onward. Moreover, upon stimulation with lipopolysaccharide (LPS) or virus, ESb-MP cells themselves produce significant amounts of MIP-1 ( approximately 200 ng/ml). Indeed, the major autocrine chemoattractants, isolated from ESb-MP cells, were intact MIP-1alpha and MIP-1beta. Pretreatment with LPS or addition of MIP-1 inhibited the in vitro migration of ESb-MP cells toward various chemokines. Moreover, compared with untreated lymphoma cells, LPS-treated cells produced significantly less metastasis in mice. The results represented here suggest that the role of chemokines in attracting tumor cells at secondary sites depends on a balance between autocrine-produced and tissue-derived chemokines. This delicate balance should be considered in the design of antichemokine strategies in different tumor types.
Menten
Patricia
P
Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium.
Saccani
Alessandra
A
Dillen
Chris
C
Wuyts
Anja
A
Struyf
Sofie
S
Proost
Paul
P
Mantovani
Alberto
A
Wang
Ji Ming
JM
Van Damme
Jo
J
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000494:pharmacology; D016399:Lymphoma, T-Cell / Q000503:physiopathology*; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D014407:Tumor Cells, Cultured
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins