Effects of tumor cell-derived interleukin 1 alpha on invasiveness of metastatic clones of murine RCT sarcoma through endothelial cells.
Interleukin 1 alpha (IL-1alpha) production and invasiveness through mouse lung endothelial cells (MLE) were investigated in high-metastatic RCT+ and low-metastatic RCT- clones established from poorly differentiated murine sarcoma. Apparently, a higher level of IL-1alpha was derived from RCT+ cells than from RCT- cells. In an invasion assay, the number of cells which penetrated the MLE monolayer in RCT+ was significantly greater than that in RCT-. The invasiveness of RCT+ and RCT- cells was stimulated by additional recombinant mouse IL-1alpha (rIL-1alpha) in a dose-dependent manner. Anti-mouse IL-1alpha monoclonal antibody (anti-IL-1alpha mAb) significantly inhibited the invasiveness of RCT+ and RCT- cells through the MLE monolayer. However, in RCT+ cells these effects were higher than in RCT- cells. In an attachment assay, the ability of RCT+ cells to attach to the MLE monolayer was significantly higher than that of RCT- cells. The attachment ability of RCT+ and RCT- cells to the MLE monolayer was significantly increased by the pretreatment with rIL-1alpha in a dose-dependent manner. In a retraction assay, conditioned medium of RCT+ stimulated the retraction of the MLE monolayer more markedly in comparison with conditioned medium of RCT-. The retraction of the MLE monolayer was stimulated by additional rIL-1alpha in a dose-dependent manner. The increased retraction of the MLE monolayer was closely associated with the enhancement in tumor cell invasiveness. These findings suggest that IL-1alpha derived from RCT+ and RCT- cells might contribute to the enhancement of tumor cell invasion by stimulating the attachment to the MLE monolayer and retraction of the MLE monolayer.
Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan.
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T
Yasuda
H
H
Matsui
M
M
Kanamori
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K
Yudoh
K
K
Ohmori
M
M
Aoki
H
H
Tsuji
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000378:metabolism* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D007375:Interleukin-1