Abstract
Chondroitin sulfate (CS) chains are secreted into the extracellular matrices or are associated with the plasma membranes of virtually all cells. They are covalently attached to the serine (Ser) residues of core proteoglycan proteins. The expression levels and/or fine structure of CS chains are altered in response to environmental cues, and such changes are involved in controlling cell fate decisions. CS chains selectively interact with numerous proteins, including growth factors, morphogens, adhesion molecules, and receptors, and regulate various cellular and/or tissue processes. These interactions between various signaling molecules and the CS moieties of proteoglycans (PGs) are the molecular basis for the functions of PGs as signaling modulators, transductors of signals into cells, and regulators of cellular functions. In addition, it is thought that the interactions between proteins and CS chains are regulated by the fine structure of CSs. The CS chains consist of N-acetylgalactosamine (GalNAc) residues alternating in glycosidic linkages with glucuronic acid residues. During the biosynthesis of CS chains, GalNAc residues are sulfated to varying degrees at the 4- and/or 6-positions. Recent studies have indicated that CS chains encode important functional information via the introduction of position-specific sulfate groups. Here, we describe the significance of CS-PGs as signal molecules or co-receptors of soluble factors such as growth factors/morphogens in cancer biology. In addition, we discuss how alterations in CS structures activate cancer-related cell signaling and lead to cancer progression.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Achur RN, Valiyaveettil M, Alkhalil A, Ockenhouse CF, Gowda DC (2000) Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta. J Biol Chem 275(51):40344–40356. https://doi.org/10.1074/jbc.M006398200
Agnelli L, Forcato M, Ferrari F, Tuana G, Todoerti K, Walker BA, Morgan GJ, Lombardi L, Bicciato S, Neri A (2011) The reconstruction of transcriptional networks reveals critical genes with implications for clinical outcome of multiple myeloma. Clin Cancer Res 17(23):7402–7412. https://doi.org/10.1158/1078-0432.CCR-11-0596
Babelova A, Moreth K, Tsalastra-Greul W, Zeng-Brouwers J, Eickelberg O, Young MF, Bruckner P, Pfeilschifter J, Schaefer RM, Grone HJ, Schaefer L (2009) Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J Biol Chem 284(36):24035–24048. https://doi.org/10.1074/jbc.M109.014266
Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA (2001) Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3(7):683–686. https://doi.org/10.1038/35083081
Bhattacharyya S, Feferman L, Tobacman JK (2017) Chondroitin sulfatases differentially regulate Wnt signaling in prostate stem cells through effects on SHP2, phospho-ERK1/2, and Dickkopf Wnt signaling pathway inhibitor (DKK3). Oncotarget 8(59):100242–100260. https://doi.org/10.18632/oncotarget.22152
Chernousov MA, Carey DJ (1993) N-syndecan (syndecan 3) from neonatal rat brain binds basic fibroblast growth factor. J Biol Chem 268(22):16810–16814
Clausen TM, Pereira MA, Al Nakouzi N, Oo HZ, Agerbaek MO, Lee S, Orum-Madsen MS, Kristensen AR, El-Naggar A, Grandgenett PM, Grem JL, Hollingsworth MA, Holst PJ, Theander T, Sorensen PH, Daugaard M, Salanti A (2016) Oncofetal chondroitin sulfate glycosaminoglycans are key players in integrin signaling and tumor cell motility. Mol Cancer Res 14(12):1288–1299. https://doi.org/10.1158/1541-7786.MCR-16-0103
Cooney CA, Jousheghany F, Yao-Borengasser A, Phanavanh B, Gomes T, Kieber-Emmons AM, Siegel ER, Suva LJ, Ferrone S, Kieber-Emmons T, Monzavi-Karbassi B (2011) Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells. Breast Cancer Res 13(3):R58. https://doi.org/10.1186/bcr2895
Cortes M, Baria AT, Schwartz NB (2009) Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate. Development 136(10):1697–1706. https://doi.org/10.1242/dev.030742
Deepa SS, Umehara Y, Higashiyama S, Itoh N, Sugahara K (2002) Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues. J Biol Chem 277(46):43707–43716. https://doi.org/10.1074/jbc.M207105200
Deepa SS, Yamada S, Zako M, Goldberger O, Sugahara K (2004) Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors. A novel function to control binding of midkine, pleiotrophin, and basic fibroblast growth factor. J Biol Chem 279(36):37368–37376. https://doi.org/10.1074/jbc.M403031200
Delehedde M, Devenyns L, Maurage CA, Vives RR (2013) Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan. Int J Cell Biol 2013:705027. https://doi.org/10.1155/2013/705027
Feferman L, Bhattacharyya S, Deaton R, Gann P, Guzman G, Kajdacsy-Balla A, Tobacman JK (2013) Arylsulfatase B (N-acetylgalactosamine-4-sulfatase): potential role as a biomarker in prostate cancer. Prostate Cancer Prostatic Dis 16(3):277–284. https://doi.org/10.1038/pcan.2013.18
Fujii M, Shibazaki Y, Wakamatsu K, Honda Y, Kawauchi Y, Suzuki K, Arumugam S, Watanabe K, Ichida T, Asakura H, Yoneyama H (2013) A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. Med Mol Morphol 46(3):141–152. https://doi.org/10.1007/s00795-013-0016-1
Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF 2nd, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ (2008) Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a. Proc Natl Acad Sci U S A 105(8):3047–3052. https://doi.org/10.1073/pnas.0712148105
Hay E, Nouraud A, Marie PJ (2009) N-cadherin negatively regulates osteoblast proliferation and survival by antagonizing Wnt, ERK and PI3K/Akt signalling. PLoS One 4(12):e8284. https://doi.org/10.1371/journal.pone.0008284
Herman D, Leakey TI, Behrens A, Yao-Borengasser A, Cooney CA, Jousheghany F, Phanavanh B, Siegel ER, Safar AM, Korourian S, Kieber-Emmons T, Monzavi-Karbassi B (2015) CHST11 gene expression and DNA methylation in breast cancer. Int J Oncol 46(3):1243–1251. https://doi.org/10.3892/ijo.2015.2828
Iida J, Dorchak J, Clancy R, Slavik J, Ellsworth R, Katagiri Y, Pugacheva EN, van Kuppevelt TH, Mural RJ, Cutler ML, Shriver CD (2015) Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth. Exp Cell Res 330(2):358–370. https://doi.org/10.1016/j.yexcr.2014.11.002
Ito Z, Takakura K, Suka M, Kanai T, Saito R, Fujioka S, Kajihara M, Yanagisawa H, Misawa T, Akiba T, Koido S, Ohkusa T (2017) Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma. Oncol Lett 13(6):4799–4805. https://doi.org/10.3892/ol.2017.6071
Jang B, Kim A, Hwang J, Song HK, Kim Y, Oh ES (2020) Emerging role of Syndecans in extracellular matrix remodeling in cancer. J Histochem Cytochem 68(12):863–870. https://doi.org/10.1369/0022155420930112
Jayne DG, Perry SL, Morrison E, Farmery SM, Guillou PJ (2000) Activated mesothelial cells produce heparin-binding growth factors: implications for tumour metastases. Br J Cancer 82(6):1233–1238. https://doi.org/10.1054/bjoc.1999.1068
Kagey MH, He X (2017) Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology. Br J Pharmacol 174(24):4637–4650. https://doi.org/10.1111/bph.13894
Karvonen H, Perttila R, Niininen W, Hautanen V, Barker H, Murumagi A, Heckman CA, Ungureanu D (2019) Wnt5a and ROR1 activate non-canonical Wnt signaling via RhoA in TCF3-PBX1 acute lymphoblastic leukemia and highlight new treatment strategies via Bcl-2 co-targeting. Oncogene 38(17):3288–3300. https://doi.org/10.1038/s41388-018-0670-9
Klemm F, Bleckmann A, Siam L, Chuang HN, Rietkotter E, Behme D, Schulz M, Schaffrinski M, Schindler S, Trumper L, Kramer F, Beissbarth T, Stadelmann C, Binder C, Pukrop T (2011) Beta-catenin-independent WNT signaling in basal-like breast cancer and brain metastasis. Carcinogenesis 32(3):434–442. https://doi.org/10.1093/carcin/bgq269
Kluppel M, Samavarchi-Tehrani P, Liu K, Wrana JL, Hinek A (2012) C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome. Eur J Hum Genet 20(8):870–877. https://doi.org/10.1038/ejhg.2012.12
Kobayashi T, Yan H, Kurahashi Y, Ito Y, Maeda H, Tada T, Hongo K, Nakayama J (2013) Role of GalNAc4S-6ST in astrocytic tumor progression. PLoS One 8(1):e54278. https://doi.org/10.1371/journal.pone.0054278
Koike T, Izumikawa T, Tamura J, Kitagawa H (2012) Chondroitin sulfate-E fine-tunes osteoblast differentiation via ERK1/2, Smad3 and Smad1/5/8 signaling by binding to N-cadherin and cadherin-11. Biochem Biophys Res Commun 420(3):523–529. https://doi.org/10.1016/j.bbrc.2012.03.024
Koziel L, Kunath M, Kelly OG, Vortkamp A (2004) Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev Cell 6(6):801–813. https://doi.org/10.1016/j.devcel.2004.05.009
Kurima K, Warman ML, Krishnan S, Domowicz M, Krueger RC Jr, Deyrup A, Schwartz NB (1998) A member of a family of sulfate-activating enzymes causes murine brachymorphism. Proc Natl Acad Sci U S A 95(15):8681–8685. https://doi.org/10.1073/pnas.95.15.8681
Le Jan S, Hayashi M, Kasza Z, Eriksson I, Bishop JR, Weibrecht I, Heldin J, Holmborn K, Jakobsson L, Soderberg O, Spillmann D, Esko JD, Claesson-Welsh L, Kjellen L, Kreuger J (2012) Functional overlap between chondroitin and heparan sulfate proteoglycans during VEGF-induced sprouting angiogenesis. Arterioscler Thromb Vasc Biol 32(5):1255–1263. https://doi.org/10.1161/ATVBAHA.111.240622
Liu CH, Lan CT, Chou JF, Tseng TJ, Liao WC (2017) CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. Cancer Lett 403:280–288. https://doi.org/10.1016/j.canlet.2017.06.023
Liu LC, Wang YL, Lin PL, Zhang X, Cheng WC, Liu SH, Chen CJ, Hung Y, Jan CI, Chang LC, Qi X, Hsieh-Wilson LC, Wang SC (2019) Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15. Int J Cancer 145(9):2478–2487. https://doi.org/10.1002/ijc.32319
MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17(1):9–26. https://doi.org/10.1016/j.devcel.2009.06.016
Maeda N, Ichihara-Tanaka K, Kimura T, Kadomatsu K, Muramatsu T, Noda M (1999) A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta. J Biol Chem 274(18):12474–12479. https://doi.org/10.1074/jbc.274.18.12474
Manon-Jensen T, Multhaupt HA, Couchman JR (2013) Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. FEBS J 280(10):2320–2331. https://doi.org/10.1111/febs.12174
Masiakowski P, Yancopoulos GD (1998) The Wnt receptor CRD domain is also found in MuSK and related orphan receptor tyrosine kinases. Curr Biol 8(12):R407. https://doi.org/10.1016/s0960-9822(98)70263-5
McCusker CD, Alfandari D (2009) Life after proteolysis: exploring the signaling capabilities of classical cadherin cleavage fragments. Commun Integr Biol 2(2):155–157
Mikami T, Kitagawa H (2013) Biosynthesis and function of chondroitin sulfate. Biochim Biophys Acta 1830(10):4719–4733. https://doi.org/10.1016/j.bbagen.2013.06.006
Muramatsu T (2010) Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases. Proc Jpn Acad Ser B Phys Biol Sci 86(4):410–425. https://doi.org/10.2183/pjab.86.410
Muramatsu T (2014) Structure and function of midkine as the basis of its pharmacological effects. Br J Pharmacol 171(4):814–826. https://doi.org/10.1111/bph.12353
Nadanaka S, Kitagawa H (2008) Heparan sulphate biosynthesis and disease. J Biochem 144(1):7–14. https://doi.org/10.1093/jb/mvn040
Nadanaka S, Ishida M, Ikegami M, Kitagawa H (2008) Chondroitin 4-O-sulfotransferase-1 modulates Wnt-3a signaling through control of E disaccharide expression of chondroitin sulfate. J Biol Chem 283(40):27333–27343. https://doi.org/10.1074/jbc.M802997200
Nadanaka S, Kinouchi H, Taniguchi-Morita K, Tamura J, Kitagawa H (2011) Down-regulation of chondroitin 4-O-sulfotransferase-1 by Wnt signaling triggers diffusion of Wnt-3a. J Biol Chem 286(6):4199–4208. https://doi.org/10.1074/jbc.M110.155093
Nadanaka S, Zhou S, Kagiyama S, Shoji N, Sugahara K, Sugihara K, Asano M, Kitagawa H (2013) EXTL2, a member of the EXT family of tumor suppressors, controls glycosaminoglycan biosynthesis in a xylose kinase-dependent manner. J Biol Chem 288(13):9321–9333. https://doi.org/10.1074/jbc.M112.416909
Nadanaka S, Kinouchi H, Kitagawa H (2016) Histone deacetylase-mediated regulation of chondroitin 4-O-sulfotransferase-1 (Chst11) gene expression by Wnt/beta-catenin signaling. Biochem Biophys Res Commun 480(2):234–240. https://doi.org/10.1016/j.bbrc.2016.10.035
Nadanaka S, Kinouchi H, Kitagawa H (2018) Chondroitin sulfate-mediated N-cadherin/beta-catenin signaling is associated with basal-like breast cancer cell invasion. J Biol Chem 293(2):444–465. https://doi.org/10.1074/jbc.M117.814509
Nadanaka S, Hashiguchi T, Kitagawa H (2020) Aberrant glycosaminoglycan biosynthesis by tumor suppressor EXTL2 deficiency promotes liver inflammation and tumorigenesis through toll-like 4 receptor signaling. FASEB J 34(6):8385–8401. https://doi.org/10.1096/fj.201902076R
Nadanaka S, Bai Y, Kitagawa H (2021) Cleavage of Syndecan-1 promotes the proliferation of the basal-like breast cancer cell line BT-549 via Akt SUMOylation. Front Cell Dev Biol 9:659428. https://doi.org/10.3389/fcell.2021.659428
Nadanaka S, Tamura JI, Kitagawa H (2022) Chondroitin sulfates control invasiveness of the basal-like breast cancer cell line MDA-MB-231 through ROR1. Front Oncol 12:914838. https://doi.org/10.3389/fonc.2022.914838
Nakanishi T, Kadomatsu K, Okamoto T, Ichihara-Tanaka K, Kojima T, Saito H, Tomoda Y, Muramatsu T (1997) Expression of syndecan-1 and -3 during embryogenesis of the central nervous system in relation to binding with midkine. J Biochem 121(2):197–205
Nguyen TL, Grizzle WE, Zhang K, Hameed O, Siegal GP, Wei S (2013) Syndecan-1 overexpression is associated with nonluminal subtypes and poor prognosis in advanced breast cancer. Am J Clin Pathol 140(4):468–474. https://doi.org/10.1309/AJCPZ1D8CALHDXCJ
Nikitovic D, Assouti M, Sifaki M, Katonis P, Krasagakis K, Karamanos NK, Tzanakakis GN (2008) Chondroitin sulfate and heparan sulfate-containing proteoglycans are both partners and targets of basic fibroblast growth factor-mediated proliferation in human metastatic melanoma cell lines. Int J Biochem Cell Biol 40(1):72–83. https://doi.org/10.1016/j.biocel.2007.06.019
Noriega-Guerra H, Freitas VM (2018) Extracellular matrix influencing HGF/c-MET signaling pathway: impact on cancer progression. Int J Mol Sci 19(11):3300. https://doi.org/10.3390/ijms19113300
Oishi I, Suzuki H, Onishi N, Takada R, Kani S, Ohkawara B, Koshida I, Suzuki K, Yamada G, Schwabe GC, Mundlos S, Shibuya H, Takada S, Minami Y (2003) The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 8(7):645–654. https://doi.org/10.1046/j.1365-2443.2003.00662.x
Owada K, Sanjo N, Kobayashi T, Mizusawa H, Muramatsu H, Muramatsu T, Michikawa M (1999) Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons. J Neurochem 73(5):2084–2092
Prabhu SV, Bhattacharyya S, Guzman-Hartman G, Macias V, Kajdacsy-Balla A, Tobacman JK (2011) Extra-lysosomal localization of arylsulfatase B in human colonic epithelium. J Histochem Cytochem 59(3):328–335. https://doi.org/10.1369/0022155410395511
Pukrop T, Klemm F, Hagemann T, Gradl D, Schulz M, Siemes S, Trumper L, Binder C (2006) Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci U S A 103(14):5454–5459. https://doi.org/10.1073/pnas.0509703103
Purnomo E, Emoto N, Nugrahaningsih DA, Nakayama K, Yagi K, Heiden S, Nadanaka S, Kitagawa H, Hirata K (2013) Glycosaminoglycan overproduction in the aorta increases aortic calcification in murine chronic kidney disease. J Am Heart Assoc 2(5):e000405. https://doi.org/10.1161/JAHA.113.000405
Purushothaman A, Fukuda J, Mizumoto S, ten Dam GB, van Kuppevelt TH, Kitagawa H, Mikami T, Sugahara K (2007) Functions of chondroitin sulfate/dermatan sulfate chains in brain development. Critical roles of E and iE disaccharide units recognized by a single chain antibody GD3G7. J Biol Chem 282(27):19442–19452. https://doi.org/10.1074/jbc.M700630200
Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P (2005) ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J 24(4):742–752. https://doi.org/10.1038/sj.emboj.7600548
Rousseau C, Ruellan AL, Bernardeau K, Kraeber-Bodere F, Gouard S, Loussouarn D, Sai-Maurel C, Faivre-Chauvet A, Wijdenes J, Barbet J, Gaschet J, Cherel M, Davodeau F (2011) Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors. EJNMMI Res 1(1):20. https://doi.org/10.1186/2191-219X-1-20
Ryan E, Shen D, Wang X (2016) Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate. FEBS J 283(8):1488–1503. https://doi.org/10.1111/febs.13686
Sakaguchi N, Muramatsu H, Ichihara-Tanaka K, Maeda N, Noda M, Yamamoto T, Michikawa M, Ikematsu S, Sakuma S, Muramatsu T (2003) Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons. Neurosci Res 45(2):219–224. https://doi.org/10.1016/s0168-0102(02)00226-2
Salanti A, Clausen TM, Agerbaek MO, Al Nakouzi N, Dahlback M, Oo HZ, Lee S, Gustavsson T, Rich JR, Hedberg BJ, Mao Y, Barington L, Pereira MA, LoBello J, Endo M, Fazli L, Soden J, Wang CK, Sander AF, Dagil R, Thrane S, Holst PJ, Meng L, Favero F, Weiss GJ, Nielsen MA, Freeth J, Nielsen TO, Zaia J, Tran NL, Trent J, Babcook JS, Theander TG, Sorensen PH, Daugaard M (2015) Targeting human cancer by a glycosaminoglycan binding malaria protein. Cancer Cell 28(4):500–514. https://doi.org/10.1016/j.ccell.2015.09.003
Saldanha J, Singh J, Mahadevan D (1998) Identification of a frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases. Protein Sci 7(8):1632–1635
Sayyad MR, Puchalapalli M, Vergara NG, Wangensteen SM, Moore M, Mu L, Edwards C, Anderson A, Kall S, Sullivan M, Dozmorov M, Singh J, Idowu MO, Koblinski JE (2019) Syndecan-1 facilitates breast cancer metastasis to the brain. Breast Cancer Res Treat 178(1):35–49. https://doi.org/10.1007/s10549-019-05347-0
Schaefer L, Babelova A, Kiss E, Hausser HJ, Baliova M, Krzyzankova M, Marsche G, Young MF, Mihalik D, Gotte M, Malle E, Schaefer RM, Grone HJ (2005) The matrix component biglycan is proinflammatory and signals through toll-like receptors 4 and 2 in macrophages. J Clin Invest 115(8):2223–2233. https://doi.org/10.1172/JCI23755
Schmidt HH, Dyomin VG, Palanisamy N, Itoyama T, Nanjangud G, Pirc-Danoewinata H, Haas OA, Chaganti RS (2004) Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32). Oncogene 23(41):6991–6996. https://doi.org/10.1038/sj.onc.1207934
Semenov M, Tamai K, He X (2005) SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280(29):26770–26775. https://doi.org/10.1074/jbc.M504308200
Sheikh MA, Kong X, Haymart B, Kaatz S, Krol G, Kozlowski J, Dahu M, Ali M, Almany S, Alexandris-Souphis T, Kline-Rogers E, Froehlich JB, Barnes GD (2021) Comparison of temporary interruption with continuation of direct oral anticoagulants for low bleeding risk procedures. Thromb Res 203:27–32. https://doi.org/10.1016/j.thromres.2021.04.006
Smith SM, West LA, Govindraj P, Zhang X, Ornitz DM, Hassell JR (2007) Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors. Matrix Biol 26(3):175–184. https://doi.org/10.1016/j.matbio.2006.10.012
Sowa H, Kaji H, Yamaguchi T, Sugimoto T, Chihara K (2002) Activations of ERK1/2 and JNK by transforming growth factor beta negatively regulate Smad3-induced alkaline phosphatase activity and mineralization in mouse osteoblastic cells. J Biol Chem 277(39):36024–36031. https://doi.org/10.1074/jbc.M206030200
Spliid CB, Toledo AG, Sanderson P, Mao Y, Gatto F, Gustavsson T, Choudhary S, Saldanha AL, Vogelsang RP, Gogenur I, Theander TG, Leach FE 3rd, Amster IJ, Esko JD, Salanti A, Clausen TM (2021) The specificity of the malarial VAR2CSA protein for chondroitin sulfate depends on 4-O-sulfation and ligand accessibility. J Biol Chem 297(6):101391. https://doi.org/10.1016/j.jbc.2021.101391
Su G, Blaine SA, Qiao D, Friedl A (2008) Membrane type 1 matrix metalloproteinase-mediated stromal syndecan-1 shedding stimulates breast carcinoma cell proliferation. Cancer Res 68(22):9558–9565. https://doi.org/10.1158/0008-5472.CAN-08-1645
Sugahara K, Schwartz NB (1979) Defect in 3′-phosphoadenosine 5′-phosphosulfate formation in brachymorphic mice. Proc Natl Acad Sci U S A 76(12):6615–6618. https://doi.org/10.1073/pnas.76.12.6615
Sugahara K, Schwartz NB (1982a) Defect in 3′-phosphoadenosine 5′-phosphosulfate synthesis in brachymorphic mice. I. Characterization of the defect. Arch Biochem Biophys 214(2):589–601. https://doi.org/10.1016/0003-9861(82)90064-9
Sugahara K, Schwartz NB (1982b) Defect in 3′-phosphoadenosine 5′-phosphosulfate synthesis in brachymorphic mice. II. Tissue distribution of the defect. Arch Biochem Biophys 214(2):602–609. https://doi.org/10.1016/0003-9861(82)90065-0
Szatmari T, Otvos R, Hjerpe A, Dobra K (2015) Syndecan-1 in cancer: implications for cell signaling, differentiation, and prognostication. Dis Markers 2015:796052. https://doi.org/10.1155/2015/796052
Thelin MA, Svensson KJ, Shi X, Bagher M, Axelsson J, Isinger-Ekstrand A, van Kuppevelt TH, Johansson J, Nilbert M, Zaia J, Belting M, Maccarana M, Malmstrom A (2012) Dermatan sulfate is involved in the tumorigenic properties of esophagus squamous cell carcinoma. Cancer Res 72(8):1943–1952. https://doi.org/10.1158/0008-5472.CAN-11-1351
Ulbricht U, Eckerich C, Fillbrandt R, Westphal M, Lamszus K (2006) RNA interference targeting protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta suppresses glioblastoma growth in vitro and in vivo. J Neurochem 98(5):1497–1506. https://doi.org/10.1111/j.1471-4159.2006.04022.x
Wang X, Zuo D, Chen Y, Li W, Liu R, He Y, Ren L, Zhou L, Deng T, Wang X, Ying G, Ba Y (2014) Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer. Br J Cancer 111(10):1965–1976. https://doi.org/10.1038/bjc.2014.493
Whalen DM, Malinauskas T, Gilbert RJ, Siebold C (2013) Structural insights into proteoglycan-shaped hedgehog signaling. Proc Natl Acad Sci U S A 110(41):16420–16425. https://doi.org/10.1073/pnas.1310097110
Willis CM, Kluppel M (2014) Chondroitin sulfate-E is a negative regulator of a pro-tumorigenic Wnt/beta-catenin-collagen 1 axis in breast cancer cells. PLoS One 9(8):e103966. https://doi.org/10.1371/journal.pone.0103966
Wu F, Zhang Y, Sun B, McMahon AP, Wang Y (2017) Hedgehog signaling: from basic biology to cancer therapy. Cell Chem Biol 24(3):252–280. https://doi.org/10.1016/j.chembiol.2017.02.010
Wu ZY, He YQ, Wang TM, Yang DW, Li DH, Deng CM, Cao LJ, Zhang JB, Xue WQ, Jia WH (2021) Glycogenes in oncofetal chondroitin sulfate biosynthesis are differently expressed and correlated with immune response in placenta and colorectal cancer. Front Cell Dev Biol 9:763875. https://doi.org/10.3389/fcell.2021.763875
Yu W, Yang L, Li T, Zhang Y (2019) Cadherin signaling in cancer: its functions and role as a therapeutic target. Front Oncol 9:989. https://doi.org/10.3389/fonc.2019.00989
Zhang S, Chen L, Cui B, Chuang HY, Yu J, Wang-Rodriguez J, Tang L, Chen G, Basak GW, Kipps TJ (2012) ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One 7(3):e31127. https://doi.org/10.1371/journal.pone.0031127
Zhao Y, Zhang D, Guo Y, Lu B, Zhao ZJ, Xu X, Chen Y (2021) Tyrosine kinase ROR1 as a target for anti-cancer therapies. Front Oncol 11:680834. https://doi.org/10.3389/fonc.2021.680834
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Nadanaka, S., Kitagawa, H. (2023). Insights into the Role of Chondroitin Sulfate in Cancer. In: Furukawa, K., Fukuda, M. (eds) Glycosignals in Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-19-7732-9_5
Download citation
DOI: https://doi.org/10.1007/978-981-19-7732-9_5
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-19-7731-2
Online ISBN: 978-981-19-7732-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)