Transient inflammatory response induced by apoptotic cells is an important mediator of melanoma cell engraftment and growth

Transient inflammatory response induced by apoptotic cells is an important mediator of melanoma cell engraftment and growth

Author Correa, Mariangela Autor UNIFESP Google Scholar
Machado, Joel Autor UNIFESP Google Scholar
Carneiro, Celia Regina Whitaker Autor UNIFESP Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Bader, M. Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Chammas, Roger Autor UNIFESP Google Scholar
Jasiulionis, Miriam Galvonas Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med
Abstract Two murine melanoma cell lines, Toil and Tm5, were derived from a nontumorigenic lineage of pigmented murine melanocytes, melan-a. Both Tm1 and Tm5 are invariably tumorigenic in syngeneic mice when inoculated s.c. in doses higher than 104 cells; 103 or fewer cells rarely give rise to tumors. We demonstrate that subtumorigenic inocula of Tint or Tm5 Cells (103) as well as of a known murine melanoma cell line (B16F10) develop as vigorously growing tumor grafts only when coinoculated with apoptotic, but not necrotic cells. the presence of apoptotic cells correlates with a transient inflammatory infiltrate, composed mainly of neutrophils and macrophages. Kinin B1 receptor-deficient mice, which have impaired transmigration of neutrophils to inflamed tissues, had significant growth inhibition of subtumorigenic doses of melanoma cells coinjected with apoptotic cells. Using the same model, tumor take in athymic mice was similar to that seen in wild-type mice, suggesting that a T cell-dependent inflammatory response is not necessary to promote the survival and growth of subtumorigenic doses of melanoma cells. Taken together, our results describe how tumor engraftment and growth can be profoundly affected by microenvironmental alterations in response to the presence of apoptotic cells. Disrupting the delicate balance between apoptotic cells and leukocyte infiltration may provide potentially important insights for understanding and interfering with tumor cell viability during treatment with either gamma-radiation or apoptosis-inducing drugs. (C) 2004 Wiley-Liss, Inc.
Keywords melanoma
tumor growth
Language English
Date 2005-04-10
Published in International Journal of Cancer. Malden: Wiley-Blackwell, v. 114, n. 3, p. 356-363, 2005.
ISSN 0020-7136 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 356-363
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000227223100004

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