Menten Patricia, Saccani Alessandra, Dillen Chris, Wuyts Anja, Struyf Sofie, Proost Paul, Mantovani Alberto, Wang Ji Ming, Van Damme Jo
Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium.
J Leukoc Biol. 2002 Oct;72(4):780-9.
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.
ESb-MP T细胞系是一种高度恶性的鼠淋巴瘤，它优先向肾脏转移。这可能是局部产生单核细胞趋化蛋白-1（MCP-1）以及在激活时受调控、正常T细胞表达和分泌的趋化因子（RANTES）的结果，这些对ESb-MP细胞具有趋化作用。在此，我们证明ESb-MP细胞从1 ng/ml起就已经对巨噬细胞炎性蛋白-1α（MIP-1α）和MIP-1β的趋化活性有反应。此外，在用脂多糖（LPS）或病毒刺激后，ESb-MP细胞自身会产生大量的MIP-1（约200 ng/ml）。实际上，从ESb-MP细胞中分离出的主要自分泌趋化因子是完整的MIP-1α和MIP-1β。用LPS预处理或添加MIP-1会抑制ESb-MP细胞在体外向各种趋化因子的迁移。此外，与未处理的淋巴瘤细胞相比，LPS处理的细胞在小鼠体内产生的转移明显更少。此处呈现的结果表明趋化因子在吸引肿瘤细胞至转移部位的作用取决于自分泌产生的趋化因子与组织来源的趋化因子之间的平衡。在设计针对不同肿瘤类型的抗趋化因子策略时应考虑这种微妙的平衡。
