Background: Tumor-associated macrophages (TAMs) constitute a major portion of the leukocyte infiltrate found in breast cancer (BC). BC cells may reprogram TAMs in a pro-angiogenic and immunosuppressive sense. We previously showed that high expression of the ID4 protein in triple-negative BC cells leads to the induction of a proangiogenic program in TAMs also through the downregulation of miR-107. Here, we investigated the expression and function of the ID4 protein in TAMs. Methods: Human macrophages obtained from peripheral blood-derived monocytes (PBDM) and mouse RAW264.7 cells were used as macrophage experimental systems. ID4-correlated mRNAs of the TCGA and E-GEOD-18295 datasets were analyzed. Results: We observed that BC cells determine a paracrine induction of ID4 expression and activation of the ID4 promoter in neighboring macrophages. Interestingly, ID4 expression is higher in macrophages associated with invasive tumor cells compared to general TAMs, and ID4-correlated mRNAs are involved in various pathways that were previously reported as relevant for TAM functions. Selective depletion of ID4 expression in macrophages enabled validation of the ability of ID4 to control the expression of YAP1 and of its downstream targets CTGF and CYR61. Conclusion: Collectively, our results show that activation of ID4 expression in TAMs is observed as a consequence of BC cell paracrine activity and could participate in macrophage reprogramming in BC.

Paracrine signaling from breast cancer cells causes activation of ID4 expression in tumor-associated macrophages / Donzelli, Sara; Sacconi, Andrea; Turco, Chiara; Gallo, Enzo; Milano, Elisa; Iosue, Ilaria; Blandino, Giovanni; Fazi, Francesco; Fontemaggi, Giulia. - In: CELLS. - ISSN 2073-4409. - 9:2(2020), pp. 1-14. [10.3390/cells9020418]

Paracrine signaling from breast cancer cells causes activation of ID4 expression in tumor-associated macrophages

Turco, Chiara;Milano, Elisa;Iosue, Ilaria;Fazi, Francesco
;
2020

Abstract

Background: Tumor-associated macrophages (TAMs) constitute a major portion of the leukocyte infiltrate found in breast cancer (BC). BC cells may reprogram TAMs in a pro-angiogenic and immunosuppressive sense. We previously showed that high expression of the ID4 protein in triple-negative BC cells leads to the induction of a proangiogenic program in TAMs also through the downregulation of miR-107. Here, we investigated the expression and function of the ID4 protein in TAMs. Methods: Human macrophages obtained from peripheral blood-derived monocytes (PBDM) and mouse RAW264.7 cells were used as macrophage experimental systems. ID4-correlated mRNAs of the TCGA and E-GEOD-18295 datasets were analyzed. Results: We observed that BC cells determine a paracrine induction of ID4 expression and activation of the ID4 promoter in neighboring macrophages. Interestingly, ID4 expression is higher in macrophages associated with invasive tumor cells compared to general TAMs, and ID4-correlated mRNAs are involved in various pathways that were previously reported as relevant for TAM functions. Selective depletion of ID4 expression in macrophages enabled validation of the ability of ID4 to control the expression of YAP1 and of its downstream targets CTGF and CYR61. Conclusion: Collectively, our results show that activation of ID4 expression in TAMs is observed as a consequence of BC cell paracrine activity and could participate in macrophage reprogramming in BC.
2020
ARNT; BLBC; CTGF; CYR61; ID4; TAMs; TNBC; Tumor-associated-macrophages; VEGFA; YAP1; breast cancer
01 Pubblicazione su rivista::01a Articolo in rivista
Paracrine signaling from breast cancer cells causes activation of ID4 expression in tumor-associated macrophages / Donzelli, Sara; Sacconi, Andrea; Turco, Chiara; Gallo, Enzo; Milano, Elisa; Iosue, Ilaria; Blandino, Giovanni; Fazi, Francesco; Fontemaggi, Giulia. - In: CELLS. - ISSN 2073-4409. - 9:2(2020), pp. 1-14. [10.3390/cells9020418]
File allegati a questo prodotto
File Dimensione Formato  
Donzelli_Paracrine_2020.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.92 MB
Formato Adobe PDF
2.92 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1386357
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 11
social impact