Abstract
Interactions of cancer cells with components of their microenvironment are crucial determinants in the decision making process which determines whether the cancer cells will progress towards a highly malignant phenotype or whether they will stay dormant or disappear altogether. The tumor microenvironment is composed of a plethora of soluble and cellular components. Many of these components deliver signals to tumor cells and thus modulate their phenotype thereby driving tumor progression. This chapter focuses on the interaction of tumor cells with endothelial cells through endothelial selectins and their fucosylated ligands expressed by the tumor cells. Comparisons are drawn between the utilization of this interaction axis by inflammatory leukocytes and by tumor cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Alexiou, D. et al. (2001). Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery. Eur. J. Cancer 37:2392–2397.
Alexiou, D. et al. (2003). Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am. J. Gastroenterol. 98: 478–485.
Becker, D.J. and Lowe, J.B. (1999). Leukocyte adhesion deficiency type II. Biochim. Biophys. Acta 1455: 193–204.
Becker, D.J. and Lowe, J.B. (2003). Fucose: biosynthesis and biological function in mammals. Glycobiology 13: 41R–53R.
Ben-Baruch, A. (2003). Host microenvironment in breast cancer development: inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor-microenvironment interactions. Breast Cancer Res. 5: 31–36.
Berthois, Y. and Martin, P. M. (1989). Growth factors and oncogenes. Biomed. Pharmacother. 43: 635–639.
Boehncke, W.H. and Schon, M.P. (2003). Interfering with leukocyte rolling-a promising therapeutic approach in inflammatory skin disorders? Trends Pharmacol. Sci. 24: 49–52.
Bruckner, K. et al. (2000). Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406: 411–415.
Burdick, M.M. et al. (2003). Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow. Am. J. Physiol Cell Physiol. 284: C977–C987.
Cambi, A. and Figdor, C.G. (2003). Dual function of C-type lectin-like receptors in the immune system. Curr. Opin. Cell Biol. 15: 539–546.
Carlow, D.A. et al. (2001). IL-2,-4, and-15 differentially regulate O-glycan branching and P-selectin ligand formation in activated CD8 T cells. J. Immunol 167: 6841–6848.
Celis, J.E. et al. (2004). Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics 3: 327–344.
Cervello, M. et al. (2000). Serum concentration of E-selectin in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 126: 345–351.
Chigira, M. et al. (1990). Autonomy in tumor cell proliferation. Med. Hypotheses 32: 249–254.
Cunha, G.R. et al. (2003). Role of the stromal microenvironment in carcinogenesis of the prostate. Int. J. Cancer 107: 1–10.
Dimitroff, C.J. et al. (2004). Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin. Cancer Res. 64: 5261–5269.
Ehrhardt, C. et al. (2004). Selectins-an emerging target for drug delivery. Adv. Drug Deliv. Rev. 56: 527–549.
Eshel, R. et al. (2000). The GPI-linked Ly-6 antigen E48 regulates expression levels of the FX enzyme and of E-selectin ligands on head and neck squamous carcinoma cells. J. Biol. Chem. 275: 12833–12840.
Eshel, R. et al. (2001). The FX enzyme is a functional component of lymphocyte activation. Cell Immunol 213: 141–148.
Eshel, R. et al. (2002a). Receptors involved in microenvironment-driven molecular evolution of cancer cells. Semin. Cancer Biol. 12: 139–147.
Eshel, R. et al. (2002b). Human Ly-6 antigen E48 (Ly-6D) regulates important interaction parameters between endothelial cells and head-and-neck squamous carcinoma cells. Int. J. Cancer 98: 803–810.
Etzioni, A. et al. (1999). Of man and mouse: leukocyte and endothelial adhesion molecule deficiencies. Blood 94: 3281–3288.
Fidler, I.J. (1995). Modulation of the organ microenvironment for the treatment of cancer metastasis (editorial). J. Natl Cancer Inst. 84: 1588–1592.
Fidler, I.J. (2002a). Critical determinants of metastasis. Semin. Cancer Biol. 12: 89–96.
Fidler, I.J. (2002b). The organ microenvironment and cancer metastasis. Differentiation 70: 498–505.
Ghia, P. et al. (2002). Chronic B cell malignancies and bone marrow microenvironment. Semin. Cancer Biol. 12: 149–155.
Halachmi, E. and Witz, I.P. (1989). Differential tumorigenicity of 3T3 cells transformed in vitro with polyoma virus and in vivo selection for high tumorigenicity. Cancer Res. 49: 2383–2389.
Haltiwanger, R.S. (2002). Regulation of signal transduction pathways in development by glycosylation. Curr. Opin. Struct. Biol. 12: 593–598.
Hanahan, D. and Weinberg, R.A. (2000). The hallmarks of cancer. Cell 100: 57–70.
Haran-Ghera, N. (1965). Autonomy and dependence of preneoplastic mammary nodules in mice. Br J. Cancer 19: 816–823.
Haroun-Bouhedja, F. et al. (2002). In vitro effects of fucans on MDA-MB231 tumor cell adhesion and invasion. Anticancer Res. 22: 2285–2292.
Hebbar, M. et al. (1998). The relationship between concentrations of circulating soluble E-selectin and clinical, pathological, and biological features in patients with breast cancer. Clin. Cancer Res. 4: 373–380.
Hebbar, M. and Peyrat, J.P. (2000). Significance of soluble endothelial molecule E-selectin in patients with breast cancer. Int. J. Biol. Markers 15: 15–21.
Hendrix, M.J. et al. (2003). Remodeling of the microenvironment by aggressive melanoma tumor cells. Ann. N. Y. Acad. Sci. 995: 151–161.
Henning, T. et al. (2004). Relevance of tumor microenvironment for progression, therapy and drug development. Anticancer Drugs 15: 7–14.
Herlyn, M. et al. (1990) Growth-regulatory factors for normal, premalignant, and malignant human cells in vitro. Adv. Cancer Res. 54: 213–234.
Hess, S.D. et al. (2003). Human CD4+ T cells present within the microenvironment of human lung tumors are mobilized by the local and sustained release of IL-12 to kill tumors in situ by indirect effects of IFN-gamma. J. Immunol. 170: 400–412.
Hiramatsu, Y. et al. (1998). Studies on selectin blockers. 6. Discovery of homologous fucose sugar unit necessary for E-selectin binding. J. Med. Chem. 41: 2302–2307.
Homeister, J. W. et al. (2001). The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing. Immunity 15: 115–126.
Honn, K.V. et al. (1992). Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev. 11: 325–351.
Ito, K. et al. (2001). Paired tumor marker of soluble E-selectin and its ligand sialyl Lewis A in colorectal cancer. J. Gastroenterol. 36: 823–829.
Izumi, Y. et al. (1995). Characterization of human colon carcinoma variant cells selected for sialyl Lex carbohydrate antigen: liver colonization and adhesion to vascular endothelial cells. Exp. Cell Res. 216: 215–221.
Jung, Y.D. et al. (2002). The role of the microenvironment and intercellular cross-talk in tumor angiogenesis. Semin. Cancer Biol. 12: 105–112.
Kannagi, R. et al. (2004). Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci. 95: 377–384.
Kenny, P.A. and Bissell, M.J. (2003). Tumor reversion: correction of malignant behavior by microenvironmental cues. Int. J. Cancer 107: 688–695.
Kiely, J.M. et al. (2003). Lipid raft localization of cell surface E-selectin is required for ligation-induced activation of phospholipase C gamma. J. Immunol. 171: 3216–3224.
Kim, Y.J. et al. (1999). Distinct selectin ligands on colon carcinoma mucins can mediate pathological interactions among platelets, leukocytes, and endothelium. Am. J. Pathol. 155: 461–472.
Laferriere, J. et al. (2002). Regulation of the metastatic process by E-selectin and stress-activated protein kinase-2/p38. Ann. N. Y. Acad. Sci. 973: 562–572.
Lebel-Binay, S. et al. (2003). IL-18 is produced by prostate cancer cells and secreted in response to interferons. Int. J. Cancer 106: 827–835.
Ley, K. (2003). The role of selectins in inflammation and disease. Trends Mol Med. 9: 263–268.
Lin, E.Y. and Pollard, J.W. (2004). Role of infiltrated leucocytes in tumour growth and spread. Br. J. Cancer 90: 2053–2058.
Liotta, L.A. and Kohn, E.C. (2001). The microenvironment of the tumour-host interface. Nature 411: 375–379.
Listinsky, J.J. et al. (2001). Cell surface fucose ablation as a therapeutic strategy for malignant neoplasms. Adv. Anat. Pathol. 8: 330–337.
Lopez-Ferrer, A. et al. (2000). Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium. Gut 47: 349–356.
Lynch, C.C. and Matrisian, L.M. (2002). Matrix metalloproteinases in tumor-host cell communication. Differentiation 70: 561–573.
Majuri, M.L. et al. (1992). Recombinant E-selectin-protein mediates tumor cell adhesion via sialyl-Le(a) and sialyl-Le(x). Biochem. Biophys. Res. Commun. 182: 1376–1382.
Magnani, J.L. (2004). The discovery, biology, and drug development of sialyl Lea and sialyl Lex. Arch. Biochem. Biophys. 426: 122–131.
Mannori, G. et al. (1995). Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Res. 55: 4425–4431.
Mantovani, A. et al. (2004). Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur. J. Cancer 40: 1660–1667.
Marquardt, T. et al. (1999). Correction of leukocyte adhesion deficiency type II with oral fucose. Blood, 94: 3976–3985.
Mathieu, S. et al. (2004). Transgene expression of alpha(1,2)-fucosyltransferase-I (FUT1) in tumor cells selectively inhibits sialyl-Lewis x expression and binding to E-selectin without affecting synthesis of sialyl-Lewis a or binding to P-selectin. Am. J. Pathol. 164: 371–383.
Middleton, J. et al. (2002). Leukocyte extravasation: chemokine transport and presentation by the endothelium. Blood 100: 3853–3860.
Moloney, D.J. et al. (2000). Fringe is a glycosyltransferase that modifies Notch. Nature 406: 369–375.
Mueller, M.M. and Fusenig, N.E. (2002). Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells. Differentiation 70: 486–497.
Niittymaki, J. et al. (2004). Cloning and expression of murine enzymes involved in the salvage pathway of GDP-L-fucose. Eur. J. Biochem. 271: 78–86.
Noble, R.L. and Hoover, L. (1975). A classification of transplantable tumors in Nb rats controlled by estrogen from dormancy to autonomy. Cancer Res. 35: 2935–2941.
Noda, K. et al. (2003). Relationship between elevated FX expression and increased production of GDP-L-fucose, a common donor substrate for fucosylation in human hepatocellular carcinoma and hepatoma cell lines. Cancer Res. 63: 6282–6289.
Nubel, T. et al. (2004). Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion. FASEB J. 18: 140–142.
O, I. et al. (2002). Role of SA-Le(a) and E-selectin in metastasis assessed with peptide antagonist. Peptides 23: 999–1010.
Ohyama, C. et al. (1998). Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells. J. Biol. Chem. 273: 14582–14587.
Ohrlein, R. (2001). Carbohydrates and derivatives as potential drug candidates with emphasis on the selectin and linear-B area. Mini Rev. Med. Chem. 1: 349–361.
Paget, S. (1889). The distribution of secondary growth in cancer of the breast, Lancet 1: 571–573.
Park, C.C. et al. (2000). The influence of the microenvironment on the malignant phenotype. Mol Med. Today 6: 324–329.
Ran, M. et al. (1992). Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells. Immunobiology 185: 415–425.
Renkonen, R. et al. (1997). In vitro experimental studies of sialyl Lewis x and sialyl Lewis a on endothelial and carcinoma cells: crucial glycans on selectin ligands. Glycoconj J. 14: 593–600.
Rosen, S.D. (2004). Ligands for L-selectin: homing, inflammation, and beyond. Annu. Rev. Immunol. 22: 129–156.
Roskelley, C.D. and Bissell, M.J. (2002). The dominance of the microenvironment in breast and ovarian cancer. Semin. Cancer Biol. 12: 97–104.
Shirahama, T. et al. (1993). The binding site for fucose-binding proteins of Lotus tetragonolobus is a prognostic marker for transitional cell carcinoma of the human urinary bladder. Cancer 72: 1329–1334.
Simon, S.I. et al. (1999). Signaling functions of L-selectin in neutrophils: alterations in the cytoskeleton and colocalization with CD18. J. Immunol. 163: 2891–2901.
Smith, P.L. et al. (2002). Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J. Cell Biol. 158: 801–815.
Sporn, M.B. and Roberts, A.B. (1985). Autocrine growth factors and cancer. Nature 313: 745–747.
Sullivan, F.X. et al. (1998). Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273: 8193–8202.
Takada, A. et al. (1991). Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem. Biophys. Res. Commun. 179: 713–719.
Taverna, D. et al. (2004). Increased primary tumor growth in mice null for beta3-or beta3/beta5-integrins or selectins. Proc. Natl. Acad. Sci. U.S.A. 101: 763–768.
Thurin, M. and Kieber-Emmons, T. (2002). SA-Lea and tumor metastasis: the old prediction and recent findings. Hybrid. Hybridomics, 21: 111–116.
Uner, A. et al. (2004). Serum levels of soluble E-selectin in colorectal cancer, Neoplasma 51: 269–274.
Ushiyama, S. et al. (1993). Structural and functional characterization of monomeric soluble P-selectin and comparison with membrane P-selectin. J. Biol. Chem. 268: 15229–15237.
Varki, A. (1994). Selectin ligands. Proc. Natl Acad. Sci. U.S.A. 91: 7390–7397.
Varki, N.M. and Varki, A. (2002). Heparin inhibition of selectin-mediated interactions during the hematogenous phase of carcinoma metastasis: rationale for clinical studies in humans. Semin. Thromb. Hemost. 28: 53–66.
Velikova, G. et al. (1998). Serum concentrations of soluble adhesion molecules in patients with colorectal cancer. Br. J. Cancer 77: 1857–1863.
Vestweber, D. (1992). Selectins: cell surface lectins which mediate the binding of leukocytes to endothelial cells. Semin. Cell Biol. 3: 211–220.
Vestweber, D. and Blanks, J.E. (1999). Mechanisms that regulate the function of the selectins and their ligands. Physiol. Rev. 79: 181–213.
Vestweber, D. (2002). Regulation of endothelial cell contacts during leukocyte extravasation. Curr. Opin. Cell Biol. 14: 587–593.
Vincent-Salomon, A. and Thiery, J.P. (2003). Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res. 5: 101–106.
Vlodavsky, I. and Friedmann, Y. (2001). Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J. Clin. Invest. 108: 341–347.
Voura, E.B. et al. (1998). Cell-cell interactions during transendothelial migration of tumor cells. Microsc. Res. Tech. 43: 265–275.
Weis, W.I. et al. (1998). The C-type lectin superfamily in the immune system. Immunol. Rev. 163: 19–34.
Wenzel, C.T. et al. (1995). Adhesion of head and neck squamous cell carcinoma to endothelial cells. The missing links. Arch. Otolaryngol. Head Neck Surg. 121: 1279–1286.
Wilson, J. and Balkwill, F. (2002). The role of cytokines in the epithelial cancer microenvironment. Semin. Cancer Biol. 12: 113–120.
Wittig, B.M. et al. (1996). Elevated serum E-selectin in patients with liver metastases of colorectal cancer. Eur. J. Cancer 32A: 1215–1218.
Witz, I.P. (1977). Tumor-bound immunoglobulins: in situ expression of humoral immunity. Adv. Cancer Res. 25: 95–148.
Witz, I.P. et al. (1996) in Premalignancy and Tumor Dormancy, edited by Yefenof, E. and Scheuermann, R.H. (R.G. Landes Company/Springer-Verlag, Heidelberg), 147–160.
Witz, I.P. (2001). Presence and functions of immune components in the tumor microenvironment. Adv. Exp. Med. Biol. 495: 317–324.
Witz, I.P. (2002). The tumour microenvironment-introduction, Semin. Cancer Biol. 12: 87–88.
Yeatman, T.J. and Nicolson, G.L. (1993). Molecular basis of tumor progression: mechanisms of organ-specific tumor metastasis. Semin. Surg. Oncol. 9: 256–263.
Yoshida, M. et al. (1998). Phosphorylation of the cytoplasmic domain of E-selectin is regulated during leukocyte-endothelial adhesion. J. Immunol. 161: 933–941.
Zhang, G.J. and Adachi, I. (1999). Serum levels of soluble intercellular adhesion molecule-1 and E-selectin in metastatic breast carcinoma: correlations with clinicopathological features and prognosis. Int. J. Oncol. 14: 71–77.
Zipin, A. et al. (2004). Tumor-microenvironment interactions: the fucose-generating FX enzyme controls adhesive properties of colorectal cancer cells. Cancer Res. 64: 6571–6578.
Zusman, T. et al. (1996a). The murine Fc-gamma (Fc gamma) receptor type II B1 is a tumorigenicity-enhancing factor in polyoma-virus-transformed 3T3 cells. Int. J. Cancer 65: 221–229.
Zusman, T. et al. (1996b). Contribution of the intracellular domain of murine Fc-gamma receptor type IIB1 to its tumor-enhancing potential. Int. J. Cancer 68: 219–227.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, Inc.
About this chapter
Cite this chapter
Witz, I.P. (2006). Tumor-Microenvironment Interactions. In: Dalgleish, A.G., Haefner, B. (eds) The Link Between Inflammation and Cancer. Cancer Treatment and Research, vol 130. Springer, Boston, MA. https://doi.org/10.1007/0-387-26283-0_6
Download citation
DOI: https://doi.org/10.1007/0-387-26283-0_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-26282-6
Online ISBN: 978-0-387-26283-3
eBook Packages: MedicineMedicine (R0)