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000178678 1001_ $$00000-0002-8638-8012$$aRuiz-Fernandez de Cordoba, Borja$$b0
000178678 245__ $$aTumor ENPP1(CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer.
000178678 260__ $$aPhiladelphia, Pa.$$c2022
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000178678 500__ $$a2022 May 2;12(5):1356-1377
000178678 520__ $$aLocoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.
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000178678 7001_ $$00000-0002-3640-8978$$aMoreno, Haritz$$b1
000178678 7001_ $$00000-0002-2882-7427$$aValencia, Karmele$$b2
000178678 7001_ $$00000-0003-0874-3389$$aPerurena, Naiara$$b3
000178678 7001_ $$aRuedas, Pablo$$b4
000178678 7001_ $$0P:(DE-He78)51635089578f68fc9efdb61e6a760b64$$aWalle, Thomas$$b5$$udkfz
000178678 7001_ $$aPezonaga-Torres, Alberto$$b6
000178678 7001_ $$00000-0003-1868-9910$$aHinojosa, Juan$$b7
000178678 7001_ $$00000-0003-0547-681X$$aGuruceaga, Elisabet$$b8
000178678 7001_ $$00000-0002-3532-8781$$aPineda-Lucena, Antonio$$b9
000178678 7001_ $$aAbengozar-Muela, Marta$$b10
000178678 7001_ $$aCochonneau, Denis$$b11
000178678 7001_ $$aZandueta, Carolina$$b12
000178678 7001_ $$aMartinez-Canarias, Susana$$b13
000178678 7001_ $$00000-0002-7339-4464$$aTeijeira, Alvaro$$b14
000178678 7001_ $$aAjona, Daniel$$b15
000178678 7001_ $$00000-0001-9192-2956$$aOrtiz-Espinosa, Sergio$$b16
000178678 7001_ $$00000-0003-0303-9958$$aMorales, Xabier$$b17
000178678 7001_ $$00000-0001-8720-0205$$aOrtiz de Solorzano, Carlos$$b18
000178678 7001_ $$00000-0003-0625-686X$$aSantisteban, Marta$$b19
000178678 7001_ $$aRamos-Garcia, Luis I$$b20
000178678 7001_ $$00000-0002-5157-8588$$aGuembe, Laura$$b21
000178678 7001_ $$aStrnad, Vratislav$$b22
000178678 7001_ $$00000-0001-7777-0669$$aHeymann, Dominique$$b23
000178678 7001_ $$00000-0003-3391-1516$$aHervas-Stubbs, Sandra$$b24
000178678 7001_ $$00000-0002-6831-6111$$aPio, Ruben$$b25
000178678 7001_ $$aRodriguez-Ruiz, Maria E$$b26
000178678 7001_ $$ade Andrea, Carlos E$$b27
000178678 7001_ $$00000-0002-9457-6881$$aVicent, Silvestre$$b28
000178678 7001_ $$aMelero, Ignacio$$b29
000178678 7001_ $$00000-0002-7289-2293$$aLecanda, Fernando$$b30
000178678 7001_ $$00000-0002-6285-4816$$aMartinez-Monge, Rafael$$b31
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