Cell Adhesion Molecules

  • Timothy Craig Allen
  • Philip T. Cagle
Part of the Molecular Pathology Library book series (MPLB, volume 2)


Cell adhesion molecules, also termed cell adhesion receptors, are one of three classes of macromolecules – along with extracellular matrix molecules and adhesion plaque proteins – that mediate cell adhesion, an activity which is critical for the commencement and maintenance of the three-dimensional structure and normal function of tissues.1,2 Cell adhesion molecules are predominantly transmembrane glycoproteins that mediate binding to extracellular matrix molecules or to associated receptors on other cells, in a manner that determines the specificity of cell–cell or cell–extracellular matrix interactions.1 There are five families of adhesion receptors – integrins, cadherins, immunoglobulin cell adhesion molecules (Ig CAMs), selectins, and CD44.1,3, 4, 5, 6, 7, 8, 9 Complexes formed by cell adhesion receptors are not static, but are dynamic units capable of obtai-ning and incorporating extracellular environmental signals, and are indeed the foundation of two-way signaling between the cell and its external environment.1,10 These cell adhesion molecule families are also involved with signaling between the interior and exterior of the cell, and as such are important in cell growth, proliferation, spatial organization, motility, migration, signaling, differentiation, apoptosis, and gene transcription in normal physiological growth and development as well as in pathological conditions such as inflammation and wound healing.5,9


Epidermal Growth Factor Receptor Cell Adhesion Molecule Focal Adhesion Kinase Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Extracellular Matrix Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998;50:197–263.PubMedGoogle Scholar
  2. 2.
    Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996;84:345–357.PubMedCrossRefGoogle Scholar
  3. 3.
    Gogali A, Charalabopoulos K, Constantopoulos S. Integrin receptors in primary lung cancer. Exp Oncol. 2004;26:106–110.PubMedGoogle Scholar
  4. 4.
    Petruzzelli L, Takami M, Humes HD. Structure and function of cell adhesion molecules. Am J Med. 1999;106:467–476.PubMedCrossRefGoogle Scholar
  5. 5.
    Nair KS, Naidoo R, Chetty R. Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value. J Clin Pathol. 2005;58:343–351.PubMedCrossRefGoogle Scholar
  6. 6.
    Charalabopoulos K, Gogali A, Kostoula OK, Constantopoulos SH. Cadherin superfamily of adhesion molecules in primary lung cancer. Exp Oncol. 2004;26:256–260.PubMedGoogle Scholar
  7. 7.
    Meyer T, Hart IR. Mechanisms of tumour metastasis. Eur J Cancer. 1998;34:214–221.PubMedCrossRefGoogle Scholar
  8. 8.
    Mousa SA. Cell adhesion molecules: potential therapeutic & diagnostic implications. Mol Biotechnol. 2008;38:33–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Lyons AJ, Jones J. Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg. 2007;36:671–679.PubMedCrossRefGoogle Scholar
  10. 10.
    Rosales C, O’Brian V, Kornberg L, Juliano RL. Signal transduction by cell adhesion receptors. Biochim Biophys Acta. 1995;1242:77–98.PubMedGoogle Scholar
  11. 11.
    Nicolson GL. Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta. 1988;948:175–224.PubMedGoogle Scholar
  12. 12.
    Hynes RO. Integrins: versatility, modulation, and signalling in cell adhesion. Cell. 1992;69:11–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Han SW, Roman J. COX-2 inhibitors suppress integrin α5 expression in human lung carcinoma cells through activation of Erk: involvement of Sp1 and AP-1 sites. Int J Cancer. 2005;116:536–546.PubMedCrossRefGoogle Scholar
  14. 14.
    Watt FM. Role of integrins in regulating epidermal adhesion, growth and differentiation. EMBO J. 2002;21:3919–3926.PubMedCrossRefGoogle Scholar
  15. 15.
    Okegawa T, Li Y, Pong RC, Hsieh JT. Cell adhesion proteins as tumor suppressors. J Urol. 2002;167:1836–1843.PubMedCrossRefGoogle Scholar
  16. 16.
    Mukhopadhyay NK, Gordon GJ, Chen CJ, et al. Activation of focal adhesion kinase in human lung cancer cells involves multiple and potentially parallel signaling events. J Cell Mol Med. 2005;9:387–397.PubMedCrossRefGoogle Scholar
  17. 17.
    Damjanovich L, Albelda SM, Mette SA. Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. Am J Respir Cell Mol Biol. 1992;6:197–206.PubMedGoogle Scholar
  18. 18.
    Hanby AN, Gilet CE, Pignatelli M, Stamp GW. Beta1 and beta4 integrin expression in metacarn and formalin fixed material from in situ ductal carcinoma of the breast. J Pathol. 1993;171:257–262.PubMedCrossRefGoogle Scholar
  19. 19.
    Kitayama J, Nayawa H, Nakayama H, et al. Functional expression of beta1 and beta2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer. J Gastroenterol. 1999;34:327–333.PubMedCrossRefGoogle Scholar
  20. 20.
    Bankhof H, Stein V, Remberger K. Differential expression of a6 and a2 very late-antigen integrins in the normal, hyperplastic and neoplastic prostate. Hum Pathol. 1993;24:243–248.CrossRefGoogle Scholar
  21. 21.
    Damkisson YP, Wilding JC, Filipe M, Hall PA, Pignatelli M. Cell–matrix interactions in gastric carcinoma. J Pathol. 1993;169:120.Google Scholar
  22. 22.
    Elenrieder V, Alder G, Gress TM. Invasion and metastasis in pancreatic cancer. Ann Oncol. 1999;4:46–50.CrossRefGoogle Scholar
  23. 23.
    Volpes R, Van der Oord J, Pesmet VJ. Distribution of the VLA family of integrins in normal and pathological human liver tissue. Gastroenterology. 1991;101:200–206.PubMedGoogle Scholar
  24. 24.
    Bichler KH, Wechsel HW. The problematic nature of metastasized cell carcinoma. Anticancer Res. 1999;19:1463–1466.PubMedGoogle Scholar
  25. 25.
    Stamb GW, Pignatelli M. Distribution of β1, α1, α2 and α3 integrin chains in basal cell carcinomas. J Pathol. 1991;103:307–313.CrossRefGoogle Scholar
  26. 26.
    Strobel T, Cannisha SA. Beta-1 integrins partly mediate binding of ovarian cancer cells to perimetral mesothelium in vitro. Gynecol Oncol. 1999;73:362–367.PubMedCrossRefGoogle Scholar
  27. 27.
    Vessey BA, Albelda S, Buck CA, et al. Distribution of integrin cell adhesion molecules in endometrial cancer. Am J Pathol. 1995;146:717–726.Google Scholar
  28. 28.
    Hehlgans S, Haase M, Cordes N. Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta. 2007;1775:163–180.PubMedGoogle Scholar
  29. 29.
    Yamada KM, Kennedy DW, Yamada SS, et al. Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. Cancer Res. 1990;50:4485–4496.PubMedGoogle Scholar
  30. 30.
    Albelda SM, Mette SA, Elder DE, et al. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990;50:6757–6764.PubMedGoogle Scholar
  31. 31.
    Hamann A, Andrew DP, Pablonski-Westrich D, Holzmann B, Butcher EC. Role of alpha-4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994;152:3282–3293.PubMedGoogle Scholar
  32. 32.
    Yednock TA, Cannon C, Fritz LC, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha-4-beta-1 integrin. Nature. 1992;356:63–66.PubMedCrossRefGoogle Scholar
  33. 33.
    Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. 1995;57:827–872.PubMedCrossRefGoogle Scholar
  34. 34.
    Hartmann TJ, Burger JA, Gloded A, Fujii N, Burger M. CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells. Oncogene. 2005;24:4462–4471.PubMedCrossRefGoogle Scholar
  35. 35.
    Dai DL, Makretsov N, Campos EI, et al. Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival. Clin Cancer Res. 2003;9:4409–4414.PubMedGoogle Scholar
  36. 36.
    Graff JR, Deddens JA, Konicek BW, et al. Integrin-linked kinase expression increases with prostate tumor grade. Clin Cancer Res. 2001;7:1987–1991.PubMedGoogle Scholar
  37. 37.
    Marotta A, Tan C, Gray V, et al. Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene. 2001;20:6250–6257.PubMedCrossRefGoogle Scholar
  38. 38.
    Takanami I. Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer. BMC Cancer. 2005;5:1.PubMedCrossRefGoogle Scholar
  39. 39.
    Dedhar S. Cell-substrate interactions and signaling through ILK. Curr Opin Cell Biol. 2000;12:250–256.PubMedCrossRefGoogle Scholar
  40. 40.
    Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol. 2001;155: 505–510.PubMedCrossRefGoogle Scholar
  41. 41.
    Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 1991;51:5054–5059.Google Scholar
  42. 42.
    Furuta SM, Ilic D, Kanazawa S, et al. Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase FAK. Oncogene. 1995;11:1989–1995.PubMedGoogle Scholar
  43. 43.
    Carelli S, Zadra G, Vaira V, et al. Up-regulation of focal adhesion kinase in non-small cell lung cancer. Lung Cancer. 2006;53:263–271.PubMedCrossRefGoogle Scholar
  44. 44.
    Sanders MA, Basson MD. Collagen IV-dependent ERK activation in human Caco-2 intestinal epithelial cells requires focal adhesion kinase. J Biol Chem. 2000;275:38040–38047.PubMedCrossRefGoogle Scholar
  45. 45.
    Guan JL, Shalloway D. Regulation of pp1256FAK both by cellular adhesion and by oncogenic transformation. Nature. 1992;358:690–692.PubMedCrossRefGoogle Scholar
  46. 46.
    Bhattacharjee A, Richards WG, Staunton J, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA. 2001;98:13790–13795.PubMedCrossRefGoogle Scholar
  47. 47.
    Yeoh EJ, Ross ME, Shurtleff SA, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002; 133-143.Google Scholar
  48. 48.
    Agochiya M, Brunton VG, Owens DW, et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene. 1999;18:5646–5653.PubMedCrossRefGoogle Scholar
  49. 49.
    Hauck CR, Hsia DA, Ilic D, Schlaepfer DD. V-Src SH3-enhanced interaction with focal adhesion kinase at beta 1 integrin-containing invadopodia promotes cell invasion. J Biol Chem. 2002;277:12487–12490.PubMedCrossRefGoogle Scholar
  50. 50.
    Hsia DA, Mitra SK, Hauck CR, et al. Differential regulation of cell motility and invasion by FAK. J Cell Biol. 2003;160:753–767.PubMedCrossRefGoogle Scholar
  51. 51.
    Sethi T, Rintoul RC, Moore SM, et al. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med. 1999;5:662–668.PubMedCrossRefGoogle Scholar
  52. 52.
    Aoudjit F, Vuori K. Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells. Oncogene 2001;20:4995–5004.PubMedCrossRefGoogle Scholar
  53. 53.
    Cordes N. Overexpression of hyperactive integrin-linked kinase leads to increased cellular radiosensitivity. Cancer Res. 2004;64:5683–5692.PubMedCrossRefGoogle Scholar
  54. 54.
    Takeichi M. Cadherin cell adhesion receptors as morphogenetic regulator. Science. 1991;251:1451–1459.PubMedCrossRefGoogle Scholar
  55. 55.
    Kemler R. From cadherins to catenins: cytoplasmic protein inte-ractions and regulation of cell adhesion. Trends Genet. 1993;9:317–321.PubMedCrossRefGoogle Scholar
  56. 56.
    Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvamorulin associates with three independent proteins structurally related in different species. EMBO J. 1989;8:1711–1717.PubMedGoogle Scholar
  57. 57.
    Hirano S, Kinoto N, Shimoyama Y, Hirohashi S, Takeichi M. Identification of a neural α-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992;70:293–301.PubMedCrossRefGoogle Scholar
  58. 58.
    Breier G, Breviario F, Caveda L, et al. Molecular cloning and expression of murine vascular endothelial cadherin in early stage development of cardiovascular system. Blood. 1996;87:630–641.PubMedGoogle Scholar
  59. 59.
    Mayer B, Johnson JP, Leitl F, et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993;53:1690–1695.PubMedGoogle Scholar
  60. 60.
    Schipper JH, Frixen UH, Behrens J, et al. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991;51:6328–6337.PubMedGoogle Scholar
  61. 61.
    Bringuier PP, Umbas R, Schaafsma HE, et al. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 1993;53:2341–2345.Google Scholar
  62. 62.
    Dorudi S, Sheffield JP, Poulsom R, Northover JM, Hart IR. E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study. Am J Pathol. 1993;142:981–986.PubMedGoogle Scholar
  63. 63.
    Oka H, Shiozaki H, Kobayashi K, et al. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993;53:1696–1701.PubMedGoogle Scholar
  64. 64.
    Ochiai A, Akimoto S, Shimoyama Y, et al. Frequent loss of α-catenin expression in scirrhous carcinomas with scattered cell growth. Jpn J Cancer Res. 1994;85:266–273.PubMedGoogle Scholar
  65. 65.
    Kadowaki T, Shiozaki H, Inoue M, et al. E-cadherin and α-catenin expression in human esophageal cancer. Cancer Res. 1994;54:291–296.PubMedGoogle Scholar
  66. 66.
    Takayama T, Shinozaki H, Shibamoto S, et al. β-Catenin expression in human cancer. Am J Pathol. 1996;148:39–46.PubMedGoogle Scholar
  67. 67.
    Benjamin JM, Nelson WJ. Bench to bedside and back again: molecular mechanisms of alpha-catenin function and roles in tumorigenesis. Semin Cancer Biol. 2008;18:53–64.PubMedCrossRefGoogle Scholar
  68. 68.
    Gavert N, Ben-Ze’ev A. Beta-catenin signaling in biological control and cancer. J Cell Biochem. 2007;1102:820–828.CrossRefGoogle Scholar
  69. 69.
    Avizienyte E, Frame MC. Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol. 2005;17:542–547.PubMedCrossRefGoogle Scholar
  70. 70.
    Hajra KM, Fearon ER. Cadherin and catenin alterations in human cancer. Genes Chromosomes Cancer. 2002;34:255–268.PubMedCrossRefGoogle Scholar
  71. 71.
    Kanai Y, Oda T, Shimoyama Y, et al. Alterations of the cadherin–catenin cell adhesion system in cancers. Princess Takamatsu Symp. 1994;24:51–62.PubMedGoogle Scholar
  72. 72.
    Watabe M, Nagafuchi A, Tsukita S, Takeichi M. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J Cell Biol. 1994;127:247–256.PubMedCrossRefGoogle Scholar
  73. 73.
    Lien WH, Klezovich O, Fernandez TE, Delrow J, Vasioukhin V. Alpha E-catenin controls cerebral cortical size by regulating the hedgehog signaling pathway. Science. 2006;311:1609–1612.PubMedCrossRefGoogle Scholar
  74. 74.
    Vasioukhin V, Bauer C, Degenstein L, Wise B, Fuchs E. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell. 2001;104:605–617.PubMedCrossRefGoogle Scholar
  75. 75.
    Kato Y, Hirano T, Yoshida K, et al. Frequent loss of E-cadherin and/or catenins in intrabronchial lesions during carcinogenesis of the bronchial epithelium. Lung Cancer. 2005;48:323–330.PubMedCrossRefGoogle Scholar
  76. 76.
    Takeichi M. Functional correlation between cell adhesive properties and some cell surface proteins. J Cell Biol. 1997;75:464–474.CrossRefGoogle Scholar
  77. 77.
    Hirano S, Nose A, Hatta K, et al. Calcium dependent cell-cell adhesion molecules (cadherins). J Cell Biol. 1987;105:2501–2510.PubMedCrossRefGoogle Scholar
  78. 78.
    Scher RL, Koch WM, Richtsmeier WJ. Induction of the intercellular adhesion molecule (ICAM-1) on squamous carcinoma by interferon gamma. Arch Otolaryngol Head Neck Surg. 1993;119:432–438.PubMedGoogle Scholar
  79. 79.
    Takeichi M. Cadherins: a molecular family important in selective cell–cell adhesion. Annu Rev Biochem. 1990;59:237–252.PubMedCrossRefGoogle Scholar
  80. 80.
    Behrens J, Mareel MM, Van Roy FM, Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell–cell adhesion. J Cell Biol. 1989;108:2435–2447.PubMedCrossRefGoogle Scholar
  81. 81.
    Frixen UH, Behrens J, Sachs M, et al. E-cadherin-mediated cell–cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991;113:173–185.PubMedCrossRefGoogle Scholar
  82. 82.
    Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, Van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991;66:107–119.PubMedCrossRefGoogle Scholar
  83. 83.
    Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153:333–339.PubMedGoogle Scholar
  84. 84.
    Akimoto S, Ochiai A, Inomata M, Hirohashi S. Expression of cadherin–catenin cell adhesion molecules, phosphorylated tyrosine residues and growth factor receptor-tyrosine kinases in gastric cancer. Jpn J Cancer Res. 1998;89:829–836.PubMedGoogle Scholar
  85. 85.
    Shimoyama Y, Nagafuchi A, Fujita S, et al. Cadherin dysfunction in a human cancer line: possible involvement of loss of α-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 1992;52:5770–5774.PubMedGoogle Scholar
  86. 86.
    Oda T, Kanai Y, Shimoyama Y, et al. Cloning of the human α-catenin cDNA and its aberrant mRNA in a human cancer cell line. Biochem Biophys Res Commun. 1993;193:897–904.PubMedCrossRefGoogle Scholar
  87. 87.
    Mattijssen V, Peters HM, Schalwijk L, et al. E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer. 1993;55:580–585.PubMedCrossRefGoogle Scholar
  88. 88.
    Umbas R, Isaacs WB, Bringuier PP, et al. Decreased E-cadherin expression is associated with poor prognosis in prostate cancer. Cancer Res. 1994;15:3929–3933.Google Scholar
  89. 89.
    Nakanishi Y, Ochiai A, Akimoto S, et al. Expression of E-cadherin, α-catenin, β-catenin, and plakoglobinin esophageal carcinomas and its prognostic significance: immunohistochemical analysis of 96 lesions. Oncology. 1997;54:158–165.PubMedCrossRefGoogle Scholar
  90. 90.
    Oyama T, Kanai Y, Ochiai A, et al. A truncated β-catenin disrupts the interaction between E-cadherin and α-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res. 1994;54:6282–6287.PubMedGoogle Scholar
  91. 91.
    Hoschuetzky H, Aberle H, Kemler R. β-Catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994;127:1375–1380.PubMedCrossRefGoogle Scholar
  92. 92.
    Ochiai A, Akimoto S, Kanai Y, et al. c-erbB-2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun. 1994;205:73–78.PubMedCrossRefGoogle Scholar
  93. 93.
    Kanai Y, Ochiai A, Shibata T, et al. c-erbB-2 gene product directly associates with β-catenin and plakoglobin. Biochem Biophys Res Commun. 1995;208:1067–1072.PubMedCrossRefGoogle Scholar
  94. 94.
    Dohadwala M, Yan SC, Luo J, et al. Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E2 induces transcriptional repressors ZEB1 and Snail in non-small cell lung cancer. Cancer Res. 2006;66:5338–5345.PubMedCrossRefGoogle Scholar
  95. 95.
    Brown JR, DuBois RN. Cyclooxygenase as a target in lung cancer. Clin Cancer Res. 2004;10:4266s–4269s.PubMedCrossRefGoogle Scholar
  96. 96.
    Dubinett SM, Sharma S, Huang M, et al. Cyclooxygenase-2 in lung cancer. Prog Exp Tumor Res. 2003;37:138–162.PubMedCrossRefGoogle Scholar
  97. 97.
    Dannenberg AJ, Zakim D. Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2. Semin Oncol. 1999;26:499–504.PubMedGoogle Scholar
  98. 98.
    Pold M, Zhu L, Sharma S, et al. Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC ligand (CXCL) 5 and interleukin 8/CXCL8 in human non-small cell lung cancer. Cancer Res. 2004;64:1853–1860.PubMedCrossRefGoogle Scholar
  99. 99.
    Hilda T, Yatabe Y, Achiwa H, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 1998;58:3761–3764.Google Scholar
  100. 100.
    Huang M, Stolina M, Sharma S, et al. Non-small cell lung cancer cyclooxygenase-2 dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res. 1998;58:1208–1216.PubMedGoogle Scholar
  101. 101.
    Sharma S, Yang SC, Zhu L, et al. Tumor cyclooxygenase-2/prostaglanding E2-dependent promotion of FOXP3expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res. 2005;65:5211–5220.PubMedCrossRefGoogle Scholar
  102. 102.
    Sharma S, Zhu L, Yang SC, et al. Cyclooxygenase 2 inhibition promotes IFN-γ-dependent enhancement of antitumor responses. J Immunol. 2005;175:813–819.PubMedGoogle Scholar
  103. 103.
    Jungck M, Grunhage F, Spengler U, et al. E-cadherin expression is homogeneously reduced in adenoma from patients with familial adenomatous polyposis: an immunohistochemical study of E-cadherin, β-catenin and cyclooxygenase-2 expression. Int J Colorectal Dis. 2004;19:438–445.PubMedCrossRefGoogle Scholar
  104. 104.
    Riedl K, Krysan K, Pold M, et al. Multifaceted roles of cyclooxygenase-2 in lung cancer. Drug Resist Updat. 2004;7:169–184.PubMedCrossRefGoogle Scholar
  105. 105.
    Cavallaro U, Christofori G. Cell adhesion and signaling by cadherins and Ig-CAMs in cancer. Natl Rev Cancer. 2004;4:118–132.Google Scholar
  106. 106.
    Choi YS, Shim YM, Kim SH, et al. Prognostic significance of E-cadherin and β-catenin in resected stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;24:441–449.PubMedCrossRefGoogle Scholar
  107. 107.
    Liu D, Huang C, Kameyama K, et al. E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer. Ann Thorac Surg. 2001;71:949–951.discussion 954-955.PubMedCrossRefGoogle Scholar
  108. 108.
    Witta SE, Gemmill RM, Hirsch FR, et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. 2006;66:944–950.PubMedCrossRefGoogle Scholar
  109. 109.
    Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small cell lung cancer (the IDEAL 1 Trial). J Clin Oncol. 2003;21:2237–2246.PubMedCrossRefGoogle Scholar
  110. 110.
    Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003;290:2149–2158.PubMedCrossRefGoogle Scholar
  111. 111.
    Shepherd FA, Rodrigues P, Jose C, et al. The National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–132.PubMedCrossRefGoogle Scholar
  112. 112.
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–1500.PubMedCrossRefGoogle Scholar
  113. 113.
    Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer – molecular and clinical predictors of outcome. N Engl J Med. 2005;353:133–144.PubMedCrossRefGoogle Scholar
  114. 114.
    Cappuzzo F, Magrini E, Ceresoli GL, et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2004;96:1133–1141.PubMedCrossRefGoogle Scholar
  115. 115.
    Ohira T, Gemmill RM, Ferguson K, et al. WNT7a induces E-cadherin in lung cancer cells. Proc Natl Acad Sci USA. 2003;100:10429–10434.PubMedCrossRefGoogle Scholar
  116. 116.
    Verschuren K, Remacle JE, Collart C, et al. SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5’-CACCT sequences in candidate target genes. J Biol Chem. 1999;27:20489–20498.CrossRefGoogle Scholar
  117. 117.
    Chinnadurai G. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell. 2002;9:213–224.PubMedCrossRefGoogle Scholar
  118. 118.
    Zhong Y, Delgado Y, Gomez J, Lee SW, Perez-Soler R. Loss of H-cadherin protein expression in human non-small cell lung cancer is associated with tumorigenicity. Clin Cancer Res. 2001;7:1683–1687.PubMedGoogle Scholar
  119. 119.
    Agiostratidou G, Julit J, Phillips GR, Hazan RB. Differential cadherin expression: potential markers for epithelial to mesenchymal transformation during tumor progression. J Mammary Gland Biol Neoplasia. 2007;12:127–133.PubMedCrossRefGoogle Scholar
  120. 120.
    Thiery JP. Epithelial–mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 2003;15:740–746.PubMedCrossRefGoogle Scholar
  121. 121.
    Kneuer C, Ehrhardt C, Radomski MW, Bakowsky U. Selectins-potential pharmacological targets. Drug Discov Today 2006;11:1034–1040.PubMedCrossRefGoogle Scholar
  122. 122.
    McEver RP. Properties of GMP-140, an inducible granule membrane protein of platelets and endothelium. Blood Cells. 1990;16:73–80.PubMedGoogle Scholar
  123. 123.
    Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood. 1994;84:2068–2101.PubMedGoogle Scholar
  124. 124.
    Springer TA. Adhesion receptors of the immune system. Nature. 1990;346:425–434.PubMedCrossRefGoogle Scholar
  125. 125.
    Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994;76:301–314.PubMedCrossRefGoogle Scholar
  126. 126.
    Lowe JB, Ward PA. Therapeutic inhibition of carbohydrate–protein interactions in vivo. J Clin Invest. 1997;100:S47–S51.PubMedGoogle Scholar
  127. 127.
    Li L, Short HJ, Qian KX, et al. Characterization of glycoprotein ligands for P-selectin on a human small cell lung cancer cell line NCI-H345. Biochem Biophys Res Commun. 2001;288:637–644.PubMedCrossRefGoogle Scholar
  128. 128.
    Tedder TF, Steeber DA, Chen A, Engle P. The selectins: vascular adhesion molecules. FASEB J. 1995;9:866–873.PubMedGoogle Scholar
  129. 129.
    Kim YG, Kim MJ, Lim JS, et al. ICAM-3-induced cancer cell proliferation through the PI3K/Akt pathway. Cancer Lett. 2006;239:103–110.PubMedCrossRefGoogle Scholar
  130. 130.
    Stone JP, Wagner DD. P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. J Clin Invest. 1993;92:804–813.PubMedCrossRefGoogle Scholar
  131. 131.
    Yu CJ, Shih JY, Lee YC, et al. Sialyl Lewis antigens: association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer. Lung Cancer. 2005;47:59–67.PubMedCrossRefGoogle Scholar
  132. 132.
    Rosen SD, Bertozzi CR. The selectins and their ligands. Curr Opin Cell Biol. 1994;6:663–673.PubMedCrossRefGoogle Scholar
  133. 133.
    Izumi Y, Taniuchi Y, Tsuji T, et al. Characterization of human colon carcinoma variant cells selected for sialyl Lex ­carbohydrate antigen: liver colonization and adhesion to vascular endothelial cells. Exp Cell Res. 1995;216:215–221.PubMedCrossRefGoogle Scholar
  134. 134.
    Laack E, Nikbakht H, Peters A, et al. Expression of CEA-CAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance. J Clin Oncol. 2002;20:4279–4284.PubMedCrossRefGoogle Scholar
  135. 135.
    D’Amico TA, Brooks KR, Joshi MBM, et al. Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection. Ann Thorac Surg. 2006;81:1982–1987.PubMedCrossRefGoogle Scholar
  136. 136.
    Rosselli M, Mineo TC, Martini F, et al. Soluble selectin levels in patients with lung cancer. Int J Biol Marker. 2002;17:56–62.Google Scholar
  137. 137.
    Tsumatori G, Ozeki Y, Takagi K, Ogata T, Tanaka S. Relation between the serum E-selectin level and the survival rate of patients with resected non-small cell lung cancers. Jpn J Cancer Res. 1999;90:301–307.PubMedGoogle Scholar
  138. 138.
    Gao Y, Wei M, Zheng S, Ba X. Chemically modified heparin inhibits the in vitro adhesion of nonsmall cell lung cancer cells to P-selectin. J Cancer Res Clin Oncol. 2006;132:257–264.PubMedCrossRefGoogle Scholar
  139. 139.
    Borsig L, Wong R, Hynes RQ, Varki NM, Varki A. synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci. USA. 2002;99:2193–2198.PubMedCrossRefGoogle Scholar
  140. 140.
    Borsig L, Wong R, Feramisco J, et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA. 2001;98:3352–3357.PubMedCrossRefGoogle Scholar
  141. 141.
    Tessier-Lavigne M, Goodman CS. The molecular biology of axon guidance. Science. 1996;274:1123–1133.PubMedCrossRefGoogle Scholar
  142. 142.
    van Buul JD, Mul FP, van der Schoot CE, Hordijk PL. ICAM-3 activation modulates cell–cell contacts of human bone marrow endothelial cells. J Vasc Res. 2004;41:28–37.PubMedCrossRefGoogle Scholar
  143. 143.
    Chung YM, Kim GB, Park CS, et al. Increased expression of ICAM3 is associated with radiation resistance in cervical cancer. Int J Cancer. 2005;117:194–201.PubMedCrossRefGoogle Scholar
  144. 144.
    Yasuda M, Tanaka Y, Tamura M, et al. Stimulation of β1 integrin down-regulates ICAM-1 expression and ICAM-1-dependent adhesion of lung cancer cells through focal adhesion kinase. Cancer Res. 2001;61:2022–2030.PubMedGoogle Scholar
  145. 145.
    Schwartz RH. Models of T cell anergy: is there a common molecular mechanism? J Exp Med. 1996;184:1–8.PubMedCrossRefGoogle Scholar
  146. 146.
    Shen J, Devery JM, King NJ. Adherence status regulates the primary cellular activation responses to the Flavivirus, West Nile. Immunology. 1995;84:254–264.PubMedGoogle Scholar
  147. 147.
    Mukai S, Kagamu H, Shu S, Plautz GE. Critical role of CD11a (LFA-1) in therapeutic efficacy of systemically transferred antitumor effector T cells. Cell Immunol. 1999;192:122–132.PubMedCrossRefGoogle Scholar
  148. 148.
    Liu YJ, Yan PS, Li J, Jia JF. Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer. World J Gastroenterol. 2005;11:6601–6606.PubMedGoogle Scholar
  149. 149.
    Liu J, Jiang G. CD44 and hematologic malignancies. Cell Mol Immunol. 2006;3:359–365.PubMedGoogle Scholar
  150. 150.
    Georgolios A, Batistatou A, Charalabopoulos A, Manolopoulos L, Charalabopoulos K. The role of CD44 adhesion molecule in oral cavity cancer. Exp Oncol. 2006;28:94–98.PubMedGoogle Scholar
  151. 151.
    Yasuda M, Nakano K, Yasumoto K, Tanaka Y. CD44: functional relevance to inflammation and malignancy. Histol Histopathol. 2002;17:945–950.PubMedGoogle Scholar
  152. 152.
    Guo, YJ, Liu G, Wang X, et al. Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. Cancer Res. 1994;54:422–426.PubMedGoogle Scholar
  153. 153.
    Adamia S, Maxwell CA, Pilarski LM. Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5:3–14.PubMedCrossRefGoogle Scholar
  154. 154.
    Wielenga VJM, Heider KH, Offerhaus JA, et al. Expression of cD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53:4754–4756.PubMedGoogle Scholar
  155. 155.
    Takahashi K, Takahashi F, Hirama M, Tanabe KK, Fukuchi Y. Restoration of CD44S in non-small cell lung cancer cells enhanced their susceptibility to the macrophage cytotoxicity. Lung Cancer. 2003;41:145–153.PubMedCrossRefGoogle Scholar
  156. 156.
    Li M, Amizuka N, Takeuchi K, et al. Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma SBC-50 cells. Micro Res Tech. 2006;69:73–83.CrossRefGoogle Scholar
  157. 157.
    Zhao Y, Sato Y, Isaji T, et al. Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J. 2008;275:1939–1948.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Texas Health Science Center at TylerTylerUSA
  2. 2.Pathology and Laboratory MedicineWeill Medical College of Cornell UniversityNew YorkUSA

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