miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major contributors of miRNAs release in blood. miRNAs modulation observed in plasma of lung cancer subjects was consistent with de-regulation of the same miRNAs observed during immunosuppressive conversion of immune cells. In particular, activated neutrophils showed a miRNA profile mirroring that observed in plasma of lung cancer subjects. Interestingly mir-320a secreted by neutrophils of high-risk heavy-smokers promoted an M2-like protumorigenic phenotype through downregulation of STAT4 when shuttled into macrophages. These findings suggest a multifactorial and nonepithelial cell-autonomous origin of circulating miRNAs associated with risk of lung cancer and that circulating miRNAs may act in paracrine signaling with causative role in lung carcinogenesis and immunosuppression.

Fortunato O., Borzi C., Milione M., Centonze G., Conte D., Boeri M., et al. (2019). Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk. INTERNATIONAL JOURNAL OF CANCER, 144(11), 2746-2761 [10.1002/ijc.31988].

Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk

Cancila V.;Tripodo C.;
2019

Abstract

miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major contributors of miRNAs release in blood. miRNAs modulation observed in plasma of lung cancer subjects was consistent with de-regulation of the same miRNAs observed during immunosuppressive conversion of immune cells. In particular, activated neutrophils showed a miRNA profile mirroring that observed in plasma of lung cancer subjects. Interestingly mir-320a secreted by neutrophils of high-risk heavy-smokers promoted an M2-like protumorigenic phenotype through downregulation of STAT4 when shuttled into macrophages. These findings suggest a multifactorial and nonepithelial cell-autonomous origin of circulating miRNAs associated with risk of lung cancer and that circulating miRNAs may act in paracrine signaling with causative role in lung carcinogenesis and immunosuppression.
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0215
Fortunato O., Borzi C., Milione M., Centonze G., Conte D., Boeri M., et al. (2019). Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk. INTERNATIONAL JOURNAL OF CANCER, 144(11), 2746-2761 [10.1002/ijc.31988].
File in questo prodotto:
File Dimensione Formato  
Circulating mir-320a.pdf

Solo gestori archvio

Tipologia: Versione Editoriale
Dimensione 1.7 MB
Formato Adobe PDF
1.7 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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: http://hdl.handle.net/10447/395010
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 39
social impact