Role of the autocrine chemokines MIP-1α and MIP-1β 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-1α (MIP-1α) and MIP-1β from 1 ng/ml onward. Moreover, upon stimulation with lipopolysaccharide (LPS) or virus, ESb-MP cells themselves produce significant amounts of MIP-1 (∼200 ng/ml). Indeed, the major autocrine chemoattractants, isolated from ESb-MP cells, were intact MIP-1α and MIP-1β. 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.