Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, has been shown to inhibit the serum-induced migration capability of highly metastatic FBJ-LL cells. In the present study, the capacity of FBJ-S1 cells to adhere to vitronectin was found to be about half that of FBJ-LL cells. Pre-treatment of FBJ-LL cells with GD1a decreased this capacity by 30% that of the control, whereas GM1-pre-treatment caused only a 10% decrease, indicating that GD1a specifically inhibits FBJ-LL cell adhesion to vitronectin. Since FBJ-LL cells contain almost no GD1a, transfectants capable of expressing GD1a to varying degrees were produced in this study by transfection of FBJ-LL cells with GM2/GD2-synthase cDNA. Decrease in the serum-induced migration capacity of these transfectants was accompanied by an increment in GD1a expression. Adhesion of the transfectants to vitronectin decreased by 30% as compared with mock-transfected cells. Within 4 to 5 weeks after GD1a-expressing transfectant and mock-transfected cells were transplanted into mice, metastatic nodules were observed in liver, lung, kidney and adrenal glands of mock-transplanted mice, but not in those with GD1a-expressing transfectants, indicating that GD1a suppresses the metastasis of FBJ-osteosarcoma cells, possibly by inhibiting cell migration and cell adhesion. The involvement of the ganglioside in the suppression of metastasis is clearly demonstrated in the present study.
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PMID:Suppression by ganglioside GD1A of migration capability, adhesion to vitronectin and metastatic potential of highly metastatic FBJ-LL cells. 1052 8

To examine the usefulness of interleukin-18 (IL-18) in the treatment of osteosarcomas, the effect of IL-18 on the growth of Dunn osteosarcoma cells was investigated. Daily intraperitoneal (i.p.) injection of mouse recombinant IL-18 (2 microg/mouse) suppressed the growth of Dunn osteosarcoma cells transplanted subcutaneously (s.c.) into syngeneic C3H mice. This IL-18-induced suppression was not affected by simultaneous treatment with anti-asialo GM1 serum, which inactivates natural killer (NK) cells. However, IL-18 failed to suppress the growth of Dunn osteosarcoma cells transplanted into BALB/c-nude mice devoid of T lymphocytes or C3H-gld/gld mice deficient in functional Fas ligand (FasL). IL-18 also failed to suppress the growth of Dunn osteosarcoma cells in vitro, although expression of IL-18 receptor mRNA and MyD88 mRNA as well as Fas mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). On the other hand, antimouse Fas antibody showed cytotoxicity against Dunn osteosarcoma cells in a dose-dependent manner in vitro. In addition, treatment of C3H mice with IL-18 enhanced the cytotoxic activity of CD8(+) T lymphocytes against Dunn osteosarcoma cells. These results indicate that IL-18 inhibits the growth of Dunn osteosarcoma cells in vivo by enhancing the cytotoxic activity of CD8(+) T lymphocytes through the FasL-Fas system.
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PMID:Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells. 1503 49

The effect of interleukin-18 (IL-18) on metastasis of highly metastatic LM8 mouse osteosarcoma cells was investigated using nude mice treated with anti-asialo GM1 serum to exclude anti-tumor actions of IL-18 through activation of T and natural killer cells. Injection of LM8 cells which do not express IL-18 receptor beta into a tail vain resulted in the formation of pulmonary and hepatic metastatic foci. Daily injection of mice with IL-18 starting the fifth day from the cell injection had no significant effect on the number of metastatic foci, while five daily injections of IL-18 before and after the cell injection resulted in marked decreases. Culture of LM8 cells with IL-18 for 5 days before the injection into mice produced no significant effect on the number of pulmonary and hepatic metastatic foci. In contrast, pretreatment of mice with IL-18 for 5 days before the cell injection markedly decreased metastatic foci. The retention of LM8 cells in the lung 24 h after their injection was also reduced by the pretreatment of mice with IL-18. Serum obtained from mice pretreated with IL-18 for 5 days suppressed mobility of LM8 cells but IL-18 itself did not. These results suggest that IL-18 inhibits metastasis of LM8 cells partly by inducing a factor(s) in the host which suppresses cell mobility.
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PMID:Effect of interleukin-18 on metastasis of mouse osteosarcoma cells. 1640 11

Osteosarcoma (OS) pulmonary metastasis translates into poor patient survival. The implication of PD-1-PD-L1 pathway in the context of NK cells and/or macrophages in OS is unknown. We investigated the effect of anti-PD-1 in OS lung metastasis and the role of NK cells and/or macrophages in anti-PD-1 responses. A human LM7 OS mouse model was used. Immunohistochemistry for tissues (PD-L1, caspase-3, Ki-67, NK cells, macrophages), and Western blotting for OS lung tumors (p-Stat3, p-Erk1/2) was performed. NK and macrophages were assessed using flow cytometry. NK cell and macrophage depletion were conducted using anti-asialo GM1 and clodrosome, respectively. PD-L1 expression was observed in human OS cells and OS patient lung metastases. Anti-PD1 antibody led to a significant decrease in the number of OS lung metastases, enhanced tumor apoptosis, decreased tumor cell proliferation, and p-STAT-3/p-Erk1/2 signaling blockade in OS lung tumors. NK cells and macrophages in OS lung tumors expressed PD-1 and anti-PD1 increased NK cell and macrophage tumor infiltration. Increased numbers of antitumor M1 macrophages and decreased pro-inflammatory M2 macrophages were seen. NK depletion did not affect therapeutic effect of anti-PD-1, suggesting that NK cells were not directly involved. However, macrophage depletion significantly compromised anti-PD1 efficacy, confirming their role in efficacy of anti-PD-1 against OS lung metastasis. Our findings suggest that OS lung metastases regression by anti-PD1 can be attributed to activated tumor M1 macrophages and reduced M2 macrophages. Owing to the co-relation of M1 macrophages with OS patient outcome, we provide a novel mechanism of PD-1 blockade and a basis for future clinical trials for anti-PD-1 antibodies in OS.
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PMID:Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases. 2973 28