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Review
. 2013 Dec 24:3:9-18.
doi: 10.2147/ITT.S32049. eCollection 2014.

Implications of chemokine receptors and inflammatory lipids in cancer

Johannes Rolin  1 , Azzam A Maghazachi  1
Affiliations
Review

Implications of chemokine receptors and inflammatory lipids in cancer

Johannes Rolin et al. Immunotargets Ther. .

Abstract

Inflammatory lipids receive much attention due to their important biological activities. Knowledge of the chemokine system has also reached a level that makes it interesting in clinics, which prompted clinical trials into compounds manipulating chemokines or their receptors. However, little attention has been devoted to understand the relations between these two systems. Here, we will review the role of inflammatory lipids and chemokines in innate and adaptive immunity with an attempt to link the two systems and with emphasis on their importance in cancer development.

Keywords: FTY720; HODE; chemokines; linoleic acid; sphingosine 1-phosphate.

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Figures

Figure 1
Figure 1
Development of tumor metastases aided by the chemokine system. The process of tumor dissemination is depicted in seven steps: 1. Adhesion/rolling of leukocytes. 2. Transmigration of leukocytes. 3. Maturation of leukocytes. 4. Retention of leukocytes 5. Malignant transformation. 6. Malignant growth. 7. Metastases.
Figure 2
Figure 2
Interactions among chemokines and inflammatory lipids. Notes: Both chemokines and inflammatory lipids receptors are coupled to G proteins. S1P1 binds S1P1–5, FTY720 binds S1P1,3,4,5, and PEG2 binds EP2 and EP4. Activity 1: CCR2, CCR5, and CCR7, as well as CXCR4 and CXCR5, contribute to the effect of FTY720-induced homing of lymphocytes. Activity 2: FTY720 through S1P receptor agonism reduced the expression of CCR1, CCR2, and CCR5 in renal parenchyma. Activity 3: Overexpression of S1P1 inhibits the migratory effect of CXCL12/SDF-1α for peripheral blood progenitor cells, and this effect is reduced upon FTY720 treatment due to downregulation of S1P1. Activity 4: The expression of CXCR4, as well as the secretion of CXCL12/SDF-1α, is increased by PGE2 on myeloid derived suppressor cells, leading to their recruitment into tumor growth sites. Activity 5: PGE2 is a prerequisite for the expression of CCR7 in monocyte derived DCs, and it enhances their migration towards lymph node associated chemokines CCL19/MIP-3β or CCL21/MIP-3α. However, the expression of CCR5 and CXCR3 in monocytes and macrophages is blocked, impeding natural killer cell-DC’s cross talk. Abbreviations: PGE2, Prostaglandin E2; EP, prostaglandin E receptor; DCs, dendritic cells; CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; SDF, stromal cell-derived factor; MDSCs, myeloid derived supressor cells; PBPCs, peripheral blood progenitor cells; S1P, sphingosine 1-phosphate.
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