How Do Cytokines Trigger Genomic Instability?

Table 1

Potential pro- and antitumorigenic roles of cytokines.

Cytokine	Protumorigenic role	Antitumorigenic role	Unspecified yet role in tumorigenesis	References
IL-1 (α and β)	Tumor growth, invasion and metastasis, mainly through the action of IL-1β in promoting local inflammatory responses as well as angiogenesis.	Restraint of tumor growth through activation of innate and specific immune effector mechanisms mainly through the action of IL-1α.		[17]
IL-2		(i) Stimulates growth, differentiation, and survival of cytotoxic T cells; (ii) Induces differentiation and proliferation of NK cells		[53]
IL-3			Stimulates the differentiation and growth of multipotent hematopoietic stem cells	[54]
IL-4	(i) Decreases the production of Th1 cells, macrophages, and IFN-gamma; (ii) Has been shown to drive dedifferentiation, mitogenesis and metastasis in rhabdomyosarcoma	Stimulation of activated B-cell and T-cell proliferation, and differentiation of CD4+ T-cells into Th2 cells	IgE and class II MHC expression on B cells	[55]
IL-5			(i) Stimulates B cell growth; (ii) Stimulates eosinophil growth and function	[56]
IL-6	(i) Promotion of tumor cell proliferation and inhibition of their apoptosis through activation of STAT-3.; (ii) Facilitation of senescence evasion in high-grade preneoplastic or cancerous cells through mechanisms of SASP.; (iii) Favours metastasis	(i) Mediator of the acute phase response; (ii) Induction of senescence in normal or low grade preneoplastic cells.		[25, 44]
IL-7		Stimulates proliferation of B cells, T cells, and NK cells	Stimulates the differentiation of multipotent hematopoietic stem cells	[57]
IL-8	Significant role in tumor growth, angiogenesis, epithelial to mesenchymal transition (EMT) and invasiveness	(i) Induction of chemotaxis in its target cells (neutrophils, granulocytes); (ii) Induction of senescence in normal or low-grade preneoplastic cells.		[43, 44]
IL-9	(i) Potential role in tumorigenesis due to antiapoptotic and growth factor activities; (ii) Deregulated IL-9 response may lead to malignant transformation through Jak/STAT activation		Regulation of hematopoietic cells	[58]
IL-10	Potential tumor promoting activity through activation of STAT3 and consequent upregulation of BCL-2 or BCL-XL antiapoptotic genes.	(i) Enhances B-cell survival, proliferation, and antibody production.; (ii) Inhibition of tumor development and progression through inhibition of NF-κB activation, TNF-α, IL-6, and IL-12.; (iii) Suppression of angiogenesis through inhibition of the tumor stroma.		[10, 59]
IL-11			(i) Regulator of haematopoiesis; (ii) Stimulation of megakaryocyte maturation	[60]
IL-12		(i) Stimulates the growth and function of T cells; (ii) Stimulates the production of IFN-γ, TNF-α; (iii) Induces cell-mediated immune responses; (iv) Exhibits antiangiogenic activity		[61]
IL-13			Induces IgE secretion	[62]
IL-14			Regulates the growth and proliferation of B cells	[63]
IL-15		(i) Stimulates growth, differentiation and survival of cytotoxic T cells; (ii) Induces differentiation and proliferation of NK cells		[53]
IL-16		Chemoattractant for certain immune cells expressing the cell surface molecule CD4.		[64]
IL-17	(i) Enhanced tumorigenic role exhibited in several cell lines in mice; (ii) Increases tumor angiogenesis; (iii) Induces increased expression of IL-6	Evidence of tumor cell growth inhibition by means of possible increased immune surveillance.		[10, 65, 66]
IL-18		(i) Induces cell-mediated immunity; (ii) Induces production of INF-γ		[67]
TNF-α	(i) Critical role in overall tumor cell survival by means of NF-κB-dependent antiapoptotic molecules.; (ii) Promotion of angiogenesis and metastasis.; (iii) Suppression of immune surveillance responses to the tumor.			[10]
IFN-γ		(i) Produced by cytotoxic CD8+ and CD4+ Th1 T cells; (ii) Exhibits an overall significant tumor inhibitory action.		[1, 7]
TGF-β	Tumor promoting role at the late stages of carcinogenesis	Tumor suppressive role in the beginning of carcinogenesis		[40]
OPN	Implicated in enhanced metastasis and invasion of tumor cells			[68]
CCL2	(i) Induces the recruitment of macrophages; (ii) Induces angiogenesis and matrix remodeling; (iii) Promotes prostate cancer cell proliferation, migration, invasion, and survival			[69]
CCL21		(i) Immune-mediated antitumor response (chemoattraction of B cells and NK cells to the lymph nodes); (ii) Angiostatic effect		[70, 71]
CCL16		Augments the cytotoxic activities of effector T cells		[72]
CXCL12	(i) Suppress antitumor immunity in the tumor microenvironment; (ii) Regulates trafficking of immature and maturing immune cells; (iii) Promotes angiogenesis; (iv) Facilitates metastasis			[73]

NK cells: Natural Killer cells; IgE: Immunoglobulin E; MHC: Major Histocompatibility Complex; OPN: Osteopontin.