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Review
. 2019 Sep 6:10:2120.
doi: 10.3389/fimmu.2019.02120. eCollection 2019.

Altered Cell Adhesion and Glycosylation Promote Cancer Immune Suppression and Metastasis

Heinz Läubli  1 , Lubor Borsig  2   3
Affiliations
Review

Altered Cell Adhesion and Glycosylation Promote Cancer Immune Suppression and Metastasis

Heinz Läubli et al. Front Immunol. .

Abstract

Cell-cell interactions and cell adhesion are key mediators of cancer progression and facilitate hallmarks of cancer including immune evasion and metastatic dissemination. Many cell adhesion molecules within the tumor microenvironment are changed and significant alterations of glycosylation are observed. These changes in cell adhesion molecules alter the ability of tumor cells to interact with other cells and extracellular matrix proteins. Three families of cell-cell interaction molecules selectins, Siglecs, and integrins have been associated with cancer progression in many pre-clinical studies, yet inhibition of cell adhesion as a therapeutic target is just beginning to be explored. We review how cell-cell interactions mediated by integrins and the glycan-binding receptors selectins and Siglec receptors support cancer progression. The discussion focuses on mechanisms during immune evasion and metastasis that can be therapeutically targeted by blocking these cell-cell interactions.

Keywords: Siglec; immunity; integrin; selectin; sialic acid; tumor microenvironment.

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Figures

Figure 1
Figure 1
Cell adhesion facilitates tumor cell survival in the circulation and tumor cell extravasation. Tumor cells in the circulation interact through selectins and integrins with blood constituents (platelets, leukocytes, and endothelial cells). (1) platelet-tumor cell aggregate formation is mediated by both P-selectin and integrins through fibrin and fibrinogen. (2) The survival of circulating tumor cells is further enhanced by aggregation with neutrophils that promote tumor cell proliferation (17). Whether L-selectin or integrins mediate these interactions remains to be determined. (3) Tumor cell interaction with the endothelium, leading to adherence, is mediated by P-and E-selectins, and tumor cell firm adhesion is facilitated by integrins, and their interaction, for example with VCAM-1 on tumor cells. (4) Tumor cell-endothelial interaction directly or facilitated by monocytes, contribute to the initiation of tumor cell extravasation. This process is dependent both on E-selectin and integrin engagement.
Figure 2
Figure 2
The sialoglycan-Siglec glyco-immune checkpoint involves cells of the innate and the adaptive immune response. Cancer-associated sialoglycans on the surface of tumor cells but also within the tumor microenvironment can mediate immune evasion by engaging Siglec receptors on cells of the innate (NK cells, myeloid cells, and macrophages) and the adaptive (T cells) immune system. Inhibitory Siglec receptors, for example Siglec-9, can inhibit T cell activation by modulating signaling of the T cell receptor. Similarly, NK cell activation and tumor cell killing can be reduced by inhibitory Siglecs such as Siglec-7 and Siglec-9. Interactions of cancer-associated sialoglycans can also regulate myeloid cells and tumor-associated macrophages by influencing the polarization of TAMs and potentially influencing macrophage-mediated phagocytosis via inhibitory Siglec receptors.
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References

    1. Strilic B, Offermanns S. Intravascular survival and extravasation of tumor cells. Cancer Cell. (2017) 32:282–93. 10.1016/j.ccell.2017.07.001 - DOI - PubMed
    1. Cooper J, Giancotti FG. Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell. (2019) 35:347–67. 10.1016/j.ccell.2019.01.007 - DOI - PMC - PubMed
    1. Vajaria BN, Patel PS. Glycosylation: a hallmark of cancer? Glycoconj J. (2017) 34:147–156. 10.1007/s10719-016-9755-2 - DOI - PubMed
    1. Hauselmann I, Borsig L. Altered tumor-cell glycosylation promotes metastasis. Front Oncol. (2014) 4:28. 10.3389/fonc.2014.00028 - DOI - PMC - PubMed
    1. Fuster MM, Esko JD. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer. (2005) 5:526–42. 10.1038/nrc1649 - DOI - PubMed

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