title: Role of the autocrine chemokines MIP-1alpha and MIP-1beta in the metastatic behavior of murine T cell lymphoma.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Menten
authors.forename: Alessandra
authors.initials: A
authors.lastname: Saccani
authors.forename: Chris
authors.initials: C
authors.lastname: Dillen
authors.forename: Anja
authors.initials: A
authors.lastname: Wuyts
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
mesh_terms: 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
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins