| Author | Werneck, Miriam B. F. | |
| Author | Abreu, Adriana Vieira de | |
| Author | Chammas, Roger | |
| Author | Viola, João P. B. | |
| Access date | 2017-11-01T15:29:45Z | |
| Available date | 2017-11-01T15:29:45Z | |
| Document date | 2011 | |
| Citation | WERNECK, Miriam B. F. et al. NFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis. Cancer Immunol Immunother, v. 60, p.537–546, 2011. | pt_BR |
| ISSN | 0340-7004 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/23026 | |
| Language | eng | pt_BR |
| Publisher | Springer Verlag (Germany) | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Câncer | pt_BR |
| Subject in Portuguese | Microambiente Tumoral | pt_BR |
| Subject in Portuguese | Fatores de Transcrição NFATC | pt_BR |
| Subject in Portuguese | Melanoma B16F10 | pt_BR |
| Title | NFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis | pt_BR |
| Type | Article | |
| DOI | 10.1007/s00262-010-0964-4 | |
| Abstract | Members of the nuclear factor of activated T cell (NFAT) family of transcription factors were originally described in T lymphocytes but later shown to be expressed in several immune and non-immune cell types. NFAT proteins can modulate cellular transformation intrinsically, and NFAT-deficient (NFAT1-/-) mice are indeed more susceptible to transformation than wild-type counterparts. However, the contribution of an NFAT1-/- microenvironment to tumor progression has not been studied. We have addressed this question by inoculating NFAT1-/- mice with B16F10 melanoma cells intravenously, an established model of tumor homing and growth. Surprisingly, NFAT1-/- animals sustained less tumor growth in the lungs after melanoma inoculation than wild-type counterparts. Even though melanoma cells equally colonize NFAT1-/- and wild-type lungs, tumors do not progress in the absence of NFAT1 expression. A massive mononuclear perivascular infiltrate and reduced expression of TGF-β in the absence of NFAT1 suggested a role for tumor-infiltrating immune cells and the cytokine milieu. However, these processes are independent of an IL-4-induced regulatory tumor microenvironment, since lack of this cytokine does not alter the phenotype in NFAT1-/- animals. Bone marrow chimera experiments meant to differentiate the contributions of stromal and infiltrating cells to tumor progression demonstrated that NFAT1-induced susceptibility to pulmonary tumor growth depends on NFAT1-expressing parenchyma rather than on bone marrow-derived cells. These results suggest an important role for NFAT1 in radio-resistant tumor-associated parenchyma, which is independent of the anti-tumor immune response and Th1 versus Th2 cytokine milieu established by the cancer cells, but able to promote site-specific tumor growth. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina. Laboratório de Oncologia Experimental. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Divisão de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Cancer | pt_BR |
| Subject | Tumor microenvironment | pt_BR |
| Subject | Melanoma B16F10 | pt_BR |
| e-ISSN | 1432-0851 | |
| Embargo date | 2030-01-01 | |
