



@article {2285,
	title = {TNF-α regulates the effects of irradiation in the mouse bone marrow microenvironment},
	journal = {PLoS ONEPLoS ONE},
	volume = {5},
	year = {2010},
	note = {Cited By (since 1996): 3Export Date: 21 November 2012Source: ScopusArt. No.: e8980doi: 10.1371/journal.pone.0008980Language of Original Document: EnglishCorrespondence Address: Cacha{\c c}o, A. S.; Angiogenesis Laboratory, Centro de Investiga{\c c}{\~a}o em Patobiologia Molecular (CIPM), Instituto Portugues de Oncologia de Francisco Gentil, Lisboa, PortugalChemicals/CAS: vasculotropin, 127464-60-2; vasculotropin A, 489395-96-2; Antibodies, Neutralizing; Matrix Metalloproteinases, 3.4.24.-; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor AReferences: Baud, V., Karin, M., Signal transduction by tumor necrosis factor and its relatives (2001) Trends Cell Biol, 11, pp. 372-377;Balkwill, F., Mantovani, A., Inflammation and cancer: Back to Virchow? (2001) Lancet, 357, pp. 539-345; 
Lejeune, F.J., R{\"u}egg, C., Recombinant human tumor necrosis factor: An efficient agent for cancer treatment (2006) Bull Cancer, 93 (8), pp. E90-100; 
Moore, R.J., Owens, D.M., Stamp, G., Arnott, C., Burke, F., Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis (1999) Nat Med, 5, pp. 828-831; 
Scott, K.A., Arnott, C.H., Robinson, S.C., Moore, R.J., Thompson, R.G., TNF-alpha regulates epithelial expression of MMP-9 and integrin alphavbeta6 during tumour promotion. A role for TNF-alpha in keratocyte migration? (2004) Oncogene, 23, pp. 6954-6966; 
Hagemann, T., Robinson, S.C., Schulz, M., Trumper, L., Balkwill, F.R., Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases (2004) Carcinogenesis, 25 (8), pp. 1543-1549; 
Yang, W.L., Godwin, A.K., Xu, X.X., Tumor necrosis factor-alpha-induced matrix proteolytic enzyme production and basement membrane remodeling by human ovarian surface epithelial cells: Molecular basis linking ovulation and cancer risk (2004) Cancer Res, 64 (4), pp. 1534-1540; 
Redondo-Mu{\~n}oz, J., Escobar-D{\'\i}az, E., Samaniego, R., Terol, M.J., Garc{\'\i}a-Marco, J.A., MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration (2006) Blood, 108 (9), pp. 3143-3151; 
Rosselli, F., Sancean, J., Gluckman, E., Abnormal lymphokine production: A novel feature of the genetic disease Fanconi anemia. In vitro and in vivo spontaneous overproduction of tumor necrosis factor α (1994) Blood, 83 (5), pp. 1216-1225; 
Dufour, C., Corcione, A., Svahn, J., Haupt, R., Poggi, V., TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro (2003) Blood, 102 (6), pp. 2053-2059; 
Kuruvilla J, Leitch HA, Vickars LM, Galbraith PF, Li CH, et al. (2003) Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor. Eur J Haematol 71(5): 396-8. Erratum in: Eur J Haematol. (2004) 72(4):306Hara, T., Ando, K., Tsurumi, H., Moriwaki, H., Excessive production of tumor necrosis factor-alpha by bone marrow T lymphocytes is essential in causing bone marrow failure in patients with aplastic anemia (2004) Eur J Haematol, 73 (1), pp. 10-16; 
Kerbauy, D.B., Deeg, H.J., Apoptosis and antiapoptotic mechanisms in the progression of myelodysplastic syndromes (2007) Exp Hematol, 35 (11), pp. 1739-1746; 
Lv, L., Kerzic, P., Lin, G., Schnatter, A.R., Bao, L., The TNF-alpha 238A polymorphism is associated with susceptibility to persistent bone marrow dysplasia following chronic exposure to benzene (2007) Leuk Res, 31 (11), pp. 1479-1485; 
Boula, A., Voulgarelis, M., Giannouli, S., Katrinakis, G., Psyllaki, M., Effect of cA2 anti.tumor necrosis factor-alpha antibody therapy on hematopoiesis of patients with myelodysplastic syndromes (2006) Clin Cancer Res, 12, pp. 3099-3108; 
Deeg, H.J., Gotlib, J., Beckham, C., Dugan, K., Holmberg, L., Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: A pilot study (2002) Leukemia, 16 (2), pp. 162-164; 
Maciejewski JP, Risitano AM, Sloand EM, Wisch L, Geller N, et al. (2002) Br J Haematol 117(1): 119-26. Erratum in: Br J Haematol (2002) 117(4):1002. Ristiano Antonio M [corrected to Risitano Antonio M]De Roos, A.J., Deeg, H.J., Davis, S., A population-based study of survival in patients with secondary myelodysplastic syndromes (MDS): Impact of type and treatment of primary cancers (2007) Cancer Causes Control, 18 (10), pp. 1199-1208; 
Malcovati, L., Nimer, S.D., Myelodysplastic syndromes: Diagnosis and Staging (2008) Cancer Control, 15 (4 SUPPL.EMENT), pp. 4-13; 
Haran-Ghera, N., Peled, A., Krautghamer, R., Resnitzky, P., Initiation and promotion in radiation-induced myeloid leukemia (1992) Leukemia, 6 (7), pp. 689-695; 
Padmanabhan, A., Baker, J.A., Zirpoli, G., Sait, S.N., Ford, L.A., Acute myeloid leukemia and myelodysplastic syndrome following breast cancer: Increased frequency of other cancers and of cancers in multiple family members (2008) Leuk Res, 32 (12), pp. 1820-1823; 
Zhang, Y., Harada, A., Bluethmann, H., Wang, J.B., Nakao, S., Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro (1995) Blood, 86 (8), pp. 2930-2937; 
Rebel, V.I., Hartnett, S., Hill, G.R., Lazo-Kallanian, S.B., Ferrara, J.L., Essential role for the p55 tumor necrosis factor receptor in regulating hematopoiesis at a stem cell level (1999) J Exp Med, 190 (10), pp. 1493-1504; 
Drutskaya, M.S., Ortiz, M., Liepinsh, D.J., Kuprash, D.V., Nedospasov, S.A., Inhibitory effects of tumor necrosis factor on hematopoiesis seen in vitro are translated to increased numbers of both committed and multipotent progenitors in TNF-deficient mice (2005) Exp Hematol, 33 (11), pp. 1348-1356; 
R{\"u}be, C.E., Wilfert, F., Uthe, D., Schmid, K.W., Knoop, R., Modulation of radiation-induced tumour necrosis factor alpha (TNF-alpha) expression in the lung tissue by pentoxifylline (2002) Radiother Oncol, 64 (2), pp. 177-187; 
Zhang, M., Qian, J., Xing, X., Kong, F.M., Zhao, L., Inhibition of the tumor necrosis factor-alpha pathway is radioprotective for the lung (2008) Clin Cancer Res, 14 (6), pp. 1868-1876; 
Daigle, J.L., Hong, J.H., Chiang, C.S., McBride, W.H., The role of tumor necrosis factor signaling pathways in the response of murine brain to irradiation (2001) Cancer Res, 61 (24), pp. 8859-8865; 
Dy, L.C., Pei, Y., Travers, J.B., Augmentation of ultraviolet B radiation-induced tumor necrosis factor production by the epidermal platelet-activating factor receptor (1999) J Biol Chem, 274 (38), pp. 26917-26921; 
M{\"u}ller, K., Meineke, V., Radiation-induced alterations in cytokine production by skin cells (2007) Exp Hematol, 35 (4 SUPPL. 1), pp. 96-104; 
Tolle, D.V., Seed, T.M., Fritz, T.E., Lombard, L.S., Poole, C.M., Acute monocytic leukemia in an irradiated Beagle (1979) Vet Pathol, 16 (2), pp. 243-254; 
Seed, T.M., Chubb, G.T., Tolle, D.V., Sequential changes in bone marrow architecture during continuous low dose gamma irradiation (1981) Scan Electron Microsc, 4, pp. 61-72; 
Sato, H., Seiki, M., Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells (1993) Oncogene, 8, pp. 395-405; 
Wielockx, B., Lannoy, K., Shapiro, S.D., Inhibition of matrix metalloproteinases blocks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapy (2001) Nat Med, 7, pp. 1202-1208; 
Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, et al. (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 31:109(5): 625-37.35Natoli G, Costanzo A, Guido F, Moretti F, Bernardo A, et al. (1998) Nuclear factor kB-independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2. J Biol Chem 273(47): 31262-72.36Barkett, M., Gilmore, T.D., Control of apoptosis by Rel/NF-kappaB transcription factors (1999) Oncogene, 18 (49), pp. 6910-6924; 
Priestley, G.V., Scott, L.M., Ulyanova, T., Papayannopoulou, T., Lack of a4 integrin expression in stem cells restricts competitive function and self-renewal activity (2006) Blood, 107, pp. 2959-2967; 
Walkley, C.R., Shea, J.M., Sims, N.A., Purton, L.E., Orkin, S.H., Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment (2007) Cell, 129 (6), pp. 1081-1095. , A; 
Walkley, C.R., Olsen, G.H., Dworkin, S., Fabb, S.A., Swann, J., A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency (2007) Cell, 129 (6), pp. 1097-1110. , B; 
Leone, G., Pagano, L., Ben-Yehuda, D., Voso, M.T., Therapy-related leukemia and myelodysplasia: Susceptibility and incidence (2007) Haematologica, 92 (10), pp. 1389-1398; 
Reza, S., Shetty, V., Dar, S., Qawi, H., Raza, A., Tumor necrosis factor-α levels decrease with anticytokine therapy in patients with myelodysplastic syndromes (1998) J Interferon Cytokine Res, 18 (10), pp. 871-877; 
Raza, A., Qawi, H., Lisak, L., Andric, T., Dar, S., Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone (2000) Blood, 95 (5), pp. 1580-1587
},
	month = {2010///},
	abstract = {Background: Secondary bone marrow (BM) myelodysplastic syndromes (MDS) are increasingly common, as a result of radio or chemotherapy administered to a majority of cancer patients. Patients with secondary MDS have increased BM cell apoptosis, which results in BM dysfunction (cytopenias), and an increased risk of developing fatal acute leukemias. In the present study we asked whether TNF-α, known to regulate cell apoptosis, could modulate the onset of secondary MDS. Principal Findings:We show that TNF-α is induced by irradiation and regulates BM cells apoptosis in vitro and in vivo. In contrast to irradiated wild type (WT) mice, TNF-α deficient (TNF-α KO) mice or WT mice treated with a TNF-α-neutralizing antibody were partially protected from the apoptotic effects of irradiation. Next we established a 3-cycle irradiation protocol, in which mice were sub-lethally irradiated once monthly over a 3 month period. In this model, irradiated WT mice presented loss of microsatellite markers on BM cells, low white blood cell (WBC) counts, reduced megakaryocyte (MK) and platelet levels (thrombocytopenia) and macrocytic anemia, phenoypes that suggest the irradiation protocol resulted in BM dysfunction with clinical features of MDS. In contrast, TNF-α KO mice were protected from the irradiation effects: BM cell apoptosis following irradiation was significantly reduced, concomitant with sustained BM MK numbers and absence of other cytopenias. Moreover, irradiated WT mice with long term (>=5 months) BM dysfunction had increased BM angiogenesis, MMPs and VEGF and NFkB p65, suggestive of disease progression. Conclusion:Taken together, our data shows that TNF-α induction following irradiation modulates BM cell apoptosis and is a crucial event in BM dysfunction, secondary MDS onset and progression. {\textcopyright} 2010 Cacha{\c c}o et al.},
	keywords = {angiogenesis, animal, animal cell, animal experiment, animal model, animal tissue, Animals, Antibodies, Neutralizing, apoptosis, article, Blood, blood cell count, Blotting, Western, bone marrow, bone marrow cell, Bone Marrow Cells, C57BL mouse, Cell Line, clinical feature, controlled study, cytokine production, disease course, drug effect, Enzyme Activation, flow cytometry, genetics, immunology, in vitro study, in vivo study, irradiation, leukocyte, leukocyte count, Leukocytes, macrocytic anemia, male, matrix metalloproteinase, Matrix Metalloproteinases, megakaryocyte, Megakaryocytes, metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, microenvironment, microsatellite marker, mouse, mouse mutant, Mus, myelodysplastic syndrome, neovascularization (pathology), Neovascularization, Pathologic, neutralizing antibody, nonhuman, Pathology, phenotype, protein expression, radiation dose, radiation exposure, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, thrombocytopenia, transcription factor RelA, tumor necrosis factor alpha, tumor necrosis factor alpha antibody, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, vascularization, vasculotropin, vasculotropin A, Western blotting, zymography},
	isbn = {19326203 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77749280454\&partnerID=40\&md5=741f4070ed47c15899f89c6d21b4e8f8},
	author = {Cacha{\c c}o, A.S. and Carvalho, T. and Santos, A.C. and Igreja, C. and Fragoso, R. and Rio, C.O. and Ferreira, M. and Serpa, J. and Correia, S. and Pinto-Do-{\'O}, P. and Dias, S.}
}
