Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Nesbit, M; Schaider, H; Miller, TH; Herlyn, M.
Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells.
J Immunol. 2001; 166(11):6483-6490
Doi: 10.4049/jimmunol.166.11.6483
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- Co-Autor*innen der Med Uni Graz
- Schaider Helmut
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- Abstract:
- Tumors commonly produce chemokines for recruitment of host cells, but the biological significance of tumor-infiltrating inflammatory cells, such as monocytes/macrophages, for disease outcome is not clear. Here, we show that all of 30 melanoma cell lines secreted monocyte chemoattractant protein-1 (MCP-1), whereas normal melanocytes did not. When low MCP-1-producing melanoma cells from a biologically early, nontumorigenic stage were transduced to overexpress the MCP-1 gene, tumor formation depended on the level of chemokine secretion and monocyte infiltration; low-level MCP-1 secretion with modest monocyte infiltration resulted in tumor formation, whereas high secretion was associated with massive monocyte/macrophage infiltration into the tumor mass, leading to its destruction within a few days after injection into mice. Tumor growth stimulated by monocytes/macrophages was due to increased angiogenesis. Vessel formation in vitro was inhibited with mAbs against TNF-alpha, which, when secreted by cocultures of melanoma cells with human monocytes, induced endothelial cells under collagen gels to form branching, tubular structures. These studies demonstrate that the biological effects of tumor-derived MCP-1 are biphasic, depending on the level of secretion. This correlates with the degree of monocytic cell infiltration, which results in increased tumor vascularization and TNF-alpha production.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Division - immunology
- Cell Movement - immunology
- Cell Survival - immunology
- Cells, Cultured - immunology
- Chemokine CCL2 - biosynthesis
- Coculture Techniques - biosynthesis
- Dose-Response Relationship, Immunologic - biosynthesis
- Humans - biosynthesis
- Macrophages - immunology
- Melanoma, Experimental - blood supply
- Mice - blood supply
- Mice, SCID - blood supply
- Monocytes - immunology
- Neoplasm Transplantation - immunology
- Neovascularization, Pathologic - immunology
- Tumor Cells, Cultured - transplantation
- Tumor Necrosis Factor-alpha - biosynthesis