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Review
. 2022 Dec 30;15(1):266.
doi: 10.3390/cancers15010266.

Theranostic Applications of Glycosaminoglycans in Metastatic Renal Cell Carcinoma

San Hue Hua  1 , Maximillian Viera  1 , George W Yip  1 , Boon Huat Bay  1
Affiliations
Review

Theranostic Applications of Glycosaminoglycans in Metastatic Renal Cell Carcinoma

San Hue Hua et al. Cancers (Basel). .

Abstract

Renal cell carcinoma (RCC) makes up the majority of kidney cancers, with a poor prognosis for metastatic RCC (mRCC). Challenges faced in the management of mRCC, include a lack of reliable prognostic markers and biomarkers for precise monitoring of disease treatment, together with the potential risk of toxicity associated with more recent therapeutic options. Glycosaminoglycans (GAGs) are a class of carbohydrates that can be categorized into four main subclasses, viz., chondroitin sulfate, hyaluronic acid, heparan sulfate and keratan sulfate. GAGs are known to be closely associated with cancer progression and modulation of metastasis by modification of the tumor microenvironment. Alterations of expression, composition and spatiotemporal distribution of GAGs in the extracellular matrix (ECM), dysregulate ECM functions and drive cancer invasion. In this review, we focus on the clinical utility of GAGs as biomarkers for mRCC (which is important for risk stratification and strategizing effective treatment protocols), as well as potential therapeutic targets that could benefit patients afflicted with advanced RCC. Besides GAG-targeted therapies that holds promise in mRCC, other potential strategies include utilizing GAGs as drug carriers and their mimetics to counter cancer progression, and enhance immunotherapy through binding and transducing signals for immune mediators.

Keywords: biomarkers; glycosaminoglycans; metastasis; renal cell carcinoma; targeted therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of the four main glycosaminoglycans (GAGs). Disaccharide monomers of Hyaluronic acid (A); Chondroitin sulfate (B); Heparan sulfate (C) and Keratan sulfate (D). The possible sulfate sites are denoted with Ri, the superscript ‘i’ indicate the Carbon position where the sulfate group is esterified; R = H or SO3H. Representative Glycosaminoglycans polysaccharides of HA, CS, HS and KS consist of repeating disaccharides monomers with various sulfation patterns (E).
Figure 2
Figure 2
Proposed mechanisms of the involvement of GAGs in cancer metastasis. In metastatic renal cancer, HA, HS and HS present on the cell surface layer promote cancer cell invasion and metastatic capabilities. (A) During metastasis, cancer cells traveling in the blood vessel adhere to the endothelial cells through the binding and interaction between cell surface CD44 and HA present in the ECM. (B) HA-bound CD44 receptors on cancer cells activates MAPK-ERK1/2 and AKT signaling pathways to promote cell adhesion, migration and invasion. CD44 also increases MMP2 and MMP9 expression and secretion to help digest and remodel ECM proteins at the metastatic site. Cell surface RHAMM, upon the binding of HA in the ECM, activates FAK-Src signaling pathways to help cancer cells migrate through the blood vessel and start colonization at the metastatic site. (C) Cell surface proteoglycan of CS and HS, such as Versican and Syndecan-1, promote cancer invasion though activating Snail, EGFR and AKT signaling pathways.
Figure 3
Figure 3
Potential therapeutic targeting GAGs for mRCC.
See this image and copyright information in PMC

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References

    1. Hsieh J.J., Purdue M.P., Signoretti S., Swanton C., Albiges L., Schmidinger M., Heng D.Y., Larkin J., Ficarra V. Renal cell carcinoma. Nat. Rev. Dis. Prim. 2017;3:17009. doi: 10.1038/nrdp.2017.9. - DOI - PMC - PubMed
    1. Rini B.I., Campbell S.C., Escudier B. Renal cell carcinoma. Lancet. 2009;373:1119–1132. doi: 10.1016/S0140-6736(09)60229-4. - DOI - PubMed
    1. Frew I.J., Moch H. A clearer view of the molecular complexity of clear cell renal cell carcinoma. Annu. Rev. Pathol. 2015;10:263–289. doi: 10.1146/annurev-pathol-012414-040306. - DOI - PubMed
    1. Surveillance E., Program E.R. SEER Stat Fact Sheets: Kidney and Renal Pelvis Cancer. National Cancer Institute; Bethesda, MD, USA: 2017.
    1. Kosary C. Kidney and renal pelvis. SEER Cancer Statistics Review, 1973–1990. National Cancer Institute; Bethesda, MD, USA: 1993.

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