NFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis

dc.creatorWerneck, Miriam B. F.
dc.creatorAbreu, Adriana Vieira de
dc.creatorChammas, Roger
dc.creatorViola, João P. B.
dc.date2017-11-01T15:29:45Z
dc.date2017-11-01T15:29:45Z
dc.date2011
dc.date.accessioned2023-09-26T20:17:49Z
dc.date.available2023-09-26T20:17:49Z
dc.identifierWERNECK, 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.
dc.identifier0340-7004
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/23026
dc.identifier10.1007/s00262-010-0964-4
dc.identifier1432-0851
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8853591
dc.descriptionMembers 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.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherSpringer Verlag (Germany)
dc.rightsrestricted access
dc.subjectCâncer
dc.subjectMicroambiente Tumoral
dc.subjectFatores de Transcrição NFATC
dc.subjectMelanoma B16F10
dc.subjectCancer
dc.subjectTumor microenvironment
dc.subjectMelanoma B16F10
dc.titleNFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis
dc.typeArticle


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