Interleukin-34 (IL-34), a cytokine produced by a wide range of cells, binds to the macrophage colony-stimulating factor receptor (M-CSFR-1) and receptor-type protein-tyrosine phosphatase zeta (PTP-z) and controls myeloid cell differentiation, proliferation and survival. various types of cancers over-express IL-34 but the role of the cytokine in colorectal cancer (CRC) remains unknown. We here investigated the expression and functional role of IL-34 in CRC. A more pronounced expression of IL-34 was seen in CRC samples as compared to matched normal/benign colonic samples and this occurred at both RNA and protein level. Immunohistochemical analysis of CRC tissue samples showed that both cancer cells and lamina propria mononuclear cells over-expressed IL-34. Additionally, CRC cells expressed both M-CSFR-1 and PTP-z, thus suggesting that CRC cells can be responsive to IL-34. Indeed, stimulation of DLD-1 cancer cells with IL-34, but not with MSCF1, enhanced the cell proliferation and cell invasion without affecting cell survival. Analysis of intracellular signals underlying the mitogenic effect of IL-34 revealed that the cytokine enhanced activation of ERK1/2 and pharmacologic inhibition of ERK1/2 abrogated IL-34-driven cell proliferation. Consistently, IL-34 knockdown in HT-29 cells with a specific IL-34 antisense oligonucleotide reduced ERK1/2 activation, cell proliferation and enhanced the susceptibility of cells to Oxaliplatin-induced death. This is the first study showing up-regulation of IL-34 in CRC and suggesting a role for this cytokine in colon tumorigenesis.

Franze, E., Dinallo, V., Rizzo, A., Di Giovangiulio, M., Bevivino, G., Stolfi, C., et al. (2018). Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue. ONCOTARGET, 9(3), 3432-3445 [10.18632/oncotarget.23289].

Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue

Franze E.;Dinallo V.;Bevivino G.;Stolfi C.
;
Ortenzi A.;Sica G.;Rossi P.
;
Monteleone G.
2018

Abstract

Interleukin-34 (IL-34), a cytokine produced by a wide range of cells, binds to the macrophage colony-stimulating factor receptor (M-CSFR-1) and receptor-type protein-tyrosine phosphatase zeta (PTP-z) and controls myeloid cell differentiation, proliferation and survival. various types of cancers over-express IL-34 but the role of the cytokine in colorectal cancer (CRC) remains unknown. We here investigated the expression and functional role of IL-34 in CRC. A more pronounced expression of IL-34 was seen in CRC samples as compared to matched normal/benign colonic samples and this occurred at both RNA and protein level. Immunohistochemical analysis of CRC tissue samples showed that both cancer cells and lamina propria mononuclear cells over-expressed IL-34. Additionally, CRC cells expressed both M-CSFR-1 and PTP-z, thus suggesting that CRC cells can be responsive to IL-34. Indeed, stimulation of DLD-1 cancer cells with IL-34, but not with MSCF1, enhanced the cell proliferation and cell invasion without affecting cell survival. Analysis of intracellular signals underlying the mitogenic effect of IL-34 revealed that the cytokine enhanced activation of ERK1/2 and pharmacologic inhibition of ERK1/2 abrogated IL-34-driven cell proliferation. Consistently, IL-34 knockdown in HT-29 cells with a specific IL-34 antisense oligonucleotide reduced ERK1/2 activation, cell proliferation and enhanced the susceptibility of cells to Oxaliplatin-induced death. This is the first study showing up-regulation of IL-34 in CRC and suggesting a role for this cytokine in colon tumorigenesis.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18 - Chirurgia Generale
English
Con Impact Factor ISI
ERK 1/2; IL-34; M-CSF-1; colorectal cancer; tumorigenesis
Franze, E., Dinallo, V., Rizzo, A., Di Giovangiulio, M., Bevivino, G., Stolfi, C., et al. (2018). Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue. ONCOTARGET, 9(3), 3432-3445 [10.18632/oncotarget.23289].
Franze, E; Dinallo, V; Rizzo, A; Di Giovangiulio, M; Bevivino, G; Stolfi, C; Caprioli, F; Colantoni, A; Ortenzi, A; Di Grazia, A; Sica, G; Sileri, Pp; Rossi, P; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/197370
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