Schmidt C, Verschueren H, Toussaint-Demylle D, van den Berg T, Kraal G, De Baetselier P
Instituut voor Moleculaire Biologie, Dienst Cellulaire Immunologie, Vrije Universiteit Brussel, Belgium.
Clin Exp Metastasis. 1994 Mar;12(2):164-74. doi: 10.1007/BF01753983.
Organ-specific metastasis of tumour cells may result from selective invasion and growth or from selective host cell responses. The present study demonstrates how selective interactions with the host affect the metastatic pattern of two murine T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous inoculation into syngeneic mice BW-14 cells preferentially colonize the kidneys, whereas BW-19 cells metastasize mainly to the spleen and the liver. The organ-specific behaviour of the two cell lines appears to be determined by a differential interaction with the spleen microenvironment. Inoculation of BW-14 cells into splenectomized mice results in increased liver colonization, indicating a negative effect of the spleen on BW-14 tumour development in the liver. Macrophages are likely to be involved in this inhibition, since inoculation of BW-14 cells into macrophage-depleted mice also leads to increased liver and spleen metastasis. In contrast, inoculation of BW-19 cells into splenectomized mice results in decreased liver metastasis, which indicates that the spleen exerts a stimulating effect on BW-19 cells. Macrophages also appear to be involved in this stimulation, since macrophage depletion causes a similar decrease in liver and spleen colonization. Hence components of the splenic microenvironment, probably macrophages, exert inhibiting or stimulating activities on BW-14 or BW-19 cells respectively, thereby determining the subsequent liver or kidney colonization.
肿瘤细胞的器官特异性转移可能源于选择性侵袭和生长,也可能源于宿主细胞的选择性反应。本研究展示了与宿主的选择性相互作用如何影响两种源自BW 5147胸腺瘤的小鼠T细胞杂交瘤系的转移模式。将BW - 14细胞静脉接种到同基因小鼠体内后,它们优先定殖于肾脏,而BW - 19细胞主要转移至脾脏和肝脏。这两种细胞系的器官特异性行为似乎是由与脾脏微环境的差异相互作用所决定的。将BW - 14细胞接种到脾切除小鼠体内会导致肝脏定殖增加,这表明脾脏对BW - 14肿瘤在肝脏中的发展具有负面影响。巨噬细胞可能参与了这种抑制作用,因为将BW - 14细胞接种到巨噬细胞耗竭的小鼠体内也会导致肝脏和脾脏转移增加。相反,将BW - 19细胞接种到脾切除小鼠体内会导致肝脏转移减少,这表明脾脏对BW - 19细胞具有刺激作用。巨噬细胞似乎也参与了这种刺激作用,因为巨噬细胞耗竭会导致肝脏和脾脏定殖出现类似的减少。因此,脾脏微环境的成分,可能是巨噬细胞,分别对BW - 14或BW - 19细胞发挥抑制或刺激活性,从而决定随后的肝脏或肾脏定殖。