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Review
. 2020 Jan 20;12(1):252.
doi: 10.3390/cancers12010252.

Role of Interleukin-34 in Cancer

Eleonora Franzè  1 , Carmine Stolfi  1 , Edoardo Troncone  1 , Patrizio Scarozza  1 , Giovanni Monteleone  1
Affiliations
Review

Role of Interleukin-34 in Cancer

Eleonora Franzè et al. Cancers (Basel). .

Abstract

Cross-talk between cancer cells and the immune cells occurring in the tumor microenvironment is crucial in promoting signals that foster tumor growth and metastasis. Both cancer cells and immune cells secrete various interleukins (IL), which, either directly or indirectly, stimulate cancer-cell proliferation, survival, and diffusion, as well as contribute to sculpt the immune microenvironment, thereby amplifying tumorigenic stimuli. IL-34, a cytokine produced by a wide range of cells, has been initially involved in the control of differentiation, proliferation, and survival of myeloid cells. More recent studies documented the overexpression of IL-34 in several cancers, such as hepatocarcinoma, osteosarcoma, multiple myeloma, colon cancer, and lung cancer, and showed that tumor cells can produce and functionally respond to this cytokine. In this review, we summarize the multiple roles of IL-34 in various cancers, with the aim to better understand the relationship between the expression of this cytokine and cancer behavior and to provide new insights for exploring a new potential therapeutic target.

Keywords: M-CSF1-R; interleukins; tumor associated macrophages; tumor microenvironment.

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Conflict of interest statement

G.M. has served as an advisory board member for ABBVIE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
IL-34-driven signaling pathways. IL-34 binds to M-CSF1-R, PTP-ζ and Sydecan-1, activating several signaling pathways that regulate major cellular functions, including differentiation, polarization, survival, proliferation cytokine/chemokine expression, motility, and migration.
Figure 2
Figure 2
Overview of the tumor promoting effects of IL-34 on its target cells. Solid arrows indicate the targets of IL-34. Dashed arrows indicate the IL-34-driven, target-related tumorigenic effects.
Figure 3
Figure 3
Schematic overview depicting the pro- and anti-tumorigenic functions of IL-34. IL-34 can exert both tumor and antitumor functions, depending on the tissue context. In some tumors, IL-34 inhibits cancer cell proliferation and/or motility, as well as monocyte-like cell differentiation. Conversely, in the majority of cases, IL-34 plays a tumor-promoting role by acting directly on transformed cells, to increase their proliferation/survival, indirectly favoring tumor-associated macrophage (TAM) differentiation, survival, and expansion.
See this image and copyright information in PMC

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