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. 2013 May 28:4:122.
doi: 10.3389/fphys.2013.00122. eCollection 2013.

YKL-40 acts as an angiogenic factor to promote tumor angiogenesis

Rong Shao  1
Affiliations

YKL-40 acts as an angiogenic factor to promote tumor angiogenesis

Rong Shao. Front Physiol. .

Abstract

A secreted glycoprotein YKL-40 also named chitinase-3-like-1 is normally expressed by multiple cell types such as macrophages, chondrocytes, and vascular smooth muscle cells. However, a prominently high level of YKL-40 was found in a wide spectrum of human diseases including cancers and chronic inflammatory diseases where it was strongly expressed by cancerous cells and infiltrating macrophages. Here, we summarized recent important findings of YKL-40 derived from cancerous cells and smooth muscle cells during tumor angiogenesis and development. YKL-40 is a potent angiogenic factor capable of stimulating tumor vascularization mediated by endothelial cells and maintaining vascular integrity supported by smooth muscle cells. In addition, YKL-40 induces FAK-MAPK signaling and up-regulates VEGF receptor 2 in endothelial cells; but a neutralizing antibody (mAY) against YKL-40 inhibits its angiogenic activity. While YKL-40 is essential for angiogenesis, little is known about its functional role in tumor-associated macrophage (TAM)-mediated tumor development. Therefore, significant efforts are urgently needed to identify pathophysiological function of YKL-40 in the dynamic interaction between tumor cells and TAMs in the tumor microenvironment, which may offer substantial mechanistic insights into tumor angiogenesis and metastasis, and also point to a therapeutic target for treatment of cancers and other diseases.

Keywords: VEGF; YKL-40; angiogenesis; neutralizing anti-YKL-40 antibody; tumor cells; tumor microenvironment; tumor-associated macrophages; vascular endothelial cells.

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Figures

Figure 1
Figure 1
A scheme for YKL-40-induced tumor angiogenesis. YKL-40 secreted from tumor cells stimulates vascular endothelial cell activation to induce tumor angiogenesis through membrane receptor coupling of syndecan-1 with integrin. YKL-40 regulates VEGF in tumor cells and both may synergistically promote endothelial cell angiogenesis. YKL-40 derived from smooth muscle cells also controls vessel stability and permeability via inducing association of N- and VE-cad with β-catenin (β-cate) expressed by smooth muscle cells and endothelial cells, respectively. TAMs participate in the vascular development probably through YKL-40, which warrants further investigation. Green balls indicate secreted YKL-40 and brown triangles represent VEGF.
Figure 2
Figure 2
YKL-40 induces angiogenic signaling in endothelial cells. YKL-40 induces the coordination of syndecan-1 (S1) and integrin αvβ3 through binding heparan sulfate chains (HS) of S1 on cell surface. The intracellular signaling pathway includes pFAK861 and downstream MAP kinase Erk 1 and 2, leading to angiogenic responses and angiogenic gene expression as well (e.g., Flk-1). Flk-1 up-regulation in turns activates the signal transduction cascade, constituting a positive feedback loop to enhance angiogenic responses. Elevated Flk-1 may also sensitize angiogenic responses to VEGF. An additional PI3K-AKT pathway participating in YKL-40-induced angiogenesis in endothelial cells warrants further investigation.
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References

    1. Baird A., Schubert D., Ling N., Guillemin R. (1988). Receptor- and heparin-binding domains of basic fibroblast growth factor. Proc. Natl. Acad. Sci. U.S.A. 85, 2324–2328 - PMC - PubMed
    1. Beauvais D. M., Burbach B. J., Rapraeger A. C. (2004). The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells. J. Cell Biol. 167, 171–181 10.1083/jcb.200404171 - DOI - PMC - PubMed
    1. Bergers G., Hanahan D. (2008). Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8, 592–603 10.1038/nrc2442 - DOI - PMC - PubMed
    1. Bergmann O. J., Johansen J. S., Klausen T. W., Mylin A. K., Kristensen J. S., Kjeldsen E., et al. (2005). High serum concentration of YKL-40 is associated with short survival in patients with acute myeloid leukemia. Clin. Cancer Res. 11, 8644–8652 10.1158/1078-0432.CCR-05-1317 - DOI - PubMed
    1. Bernfield M., Gotte M., Park P. W., Reizes O., Fitzgerald M. L., Lincecum J., et al. (1999). Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68, 729–777 10.1146/annurev.biochem.68.1.729 - DOI - PubMed

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