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.
Yasuda
T
T
Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Matsui
H
H
Kanamori
M
M
Yudoh
K
K
Ohmori
K
K
Aoki
M
M
Tsuji
H
H
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