Abstract
Under normal homeostasis, melanocyte growth and behaviour is tightly controlled by the surrounding keratinocytes. Keratinocytes regulate melanocyte behaviour through a complex system of paracrine growth factors and cell–cell adhesion molecules. Pathological changes, leading to development of malignant melanoma, upset this delicate homeostatic balance and can lead to altered expression of cell–cell adhesion and cell–cell communication molecules. In particular, there is a switch from the E-cadherin-mediated keratinocyte–melanocyte partnership to the N-cadherin-mediated melanoma–melanoma and melanoma–fibroblast interaction. Other changes include the alteration in the gap junctions formed between the melanocyte and keratinocyte. Changes in the connexin expression, in particular the loss of connexin 43, may result in a reduction or a loss of gap junctional activity, which is thought to contribute towards tumour progression. In the current review we describe the alterations in cell–cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.
Similar content being viewed by others
References
Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev 1: 46–54.
Brandner JM, Kief S, Grund C, Rendl M, Houdek P, Kuhn C, Tschachler E, Franke WW, Moll I (2002) Organization and formation of the tight junction-system in human epidermis and cultured keratinocytes. Eur J Cell Biol 81: 253–263.
Brandner JM, McIntyre M, Kief S, Wladykowski E, Moll I (2003) Expression and localization of tight junction-associated proteins in human hair follicles. Arch Dermatol Res 295: 211–221.
Brissette JL, Kumar NM, Gilula NB, Hall JE, Dotto GP (1994) Switch in gap junction protein expression is associated with selective changes in junctional permeability during keratinocyte differentiation. Proc Natl Acad Sci USA 91: 6453–6457.
Burrows FJ, Gore M, Smiley WR, Kanemitsu MY, Jolly DJ, Read SB, Nicholas T, Kruse CA (2002) Purified herpes simplex virus thymidine kinase retroviral particles: III. Characterization of bystander killing mechanisms in transfected tumor cells. Cancer Gene Ther 9: 87–95.
Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2: 76–83.
Carystinos GD, Bier A, Batist G (2001) The role of connexin-mediated cell–cell communication in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6: 431–440.
Chidgey M (2002) Desmosomes and disease: An update. Histol Histopathol 17: 1179–1192.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417: 949–954.
Dejana E (1996) Endothelial adherens junctions: Implications in the control of vascular permeability and angiogenesis. J Clin Invest 100(Suppl. 11): S7–S10.
DeLuca SM, Gerhart J, Cochran E, Simak E, Blitz J, Mattiacci-Paessler M, Knudsen K, George-Weinstein M (1999) Hepatocyte growth factor/ scatter factor promotes a switch from E to N-cadherin in chick embryo epiblast cells. Exp Cell Res 251: 3–15.
Di WL, Rugg EL, Leigh IM, Kelsell DP (2001) Multiple epidermal connexins are expressed in different keratinocyte subpopulations including connexin 31. J Invest Dermatol 117: 958–964.
Donatien P, Surleve-Bazeille JE, Thody AJ, Taieb A (1993) Growth and differentiation of normal human melanocytes in a TPA-free, cholera toxin-free, low-serum medium and influence of keratinocytes. Arch Dermatol Res 285: 385–392.
Duflot-Dancer A, Mesnil M, Yamasaki H (1997) Dominant-negative abrogation of connexin-mediated cell growth control by mutant connexin genes. Oncogene 15: 2151–2158.
Eghbali B, Kessler JA, Reid LM, Roy C, Spray DC (1991) Involvement of gap junctions in tumorigenesis: Transfection of tumor cells with connexin 32 cDNA retards growth in vivo. Proc Natl Acad Sci USA 88: 10701–10705.
Elfgang C, Echert R, Lichtenbert-Frate H, Butterweck A, Traub O, Klein RA, Hülser DF, Willecke K (1995) Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J Cell Biol 129: 805–817.
Elias PM, Friend DS (1975) The permeability barrier in mammalian epidermis. J Cell Biol 65: 180–191.
Elias PM, McNutt NS, Friend DS (1977) Membrane alterations during cornification of mammalian squamous epithelia: A freeze-fracture, tracer, and thin-section study. Anat Rec 189: 577–594.
Evans WH, Martin PE (2002) Gap junctions: Structure and function. Mol Membr Biol 19: 121–136.
Franke WW, Goldschmidt MD, Zimbelmann R, Mueller HM, Schiller DL, Cowin P (1989) Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci USA 86: 4027–4031
Fukata M, Kuroda S, Nakagawa M, Kawajiri A, Itoh N, Shoji I, Matsuura Y, Yonehara S, Fujisawa H, Kikuchi A, Kaibuchi K (1999a) Cdc42 and Rac1 regulate the interaction of IQGAP1 with beta-catenin. J Biol Chem 274: 26044–26050.
Fukata M, Nakagawa M, Kuroda S, Kaibuchi K (1999b) Cell adhesion and Rho small GTPases. J Cell Sci 112: 4491–4500.
Funayama N, Fagotto F, McCrea P, Gumbiner BM (1995) Embryonic axis induction by the armadillo repeat domain of β-catenin: Evidence for intracellular signaling. J Cell Biol 128: 959–968.
Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice. J Cell Biol 156: 1099–1111.
Goliger JA, Paul DL (1995) Wounding alters epidermal connexin expression and gap junction-mediated intercellular communication. Mol Biol Cell 6: 1491–1501.
Guilford P (1999) E-cadherin downregulation in cancer: Fuel on the fire? Mol Med Today 5: 172–177.
Haass NK, Houdek P, Brandner JM, Moll I (2003a) Expression patterns of connexins in Merkel cell carcinoma and adjacent epidermis. In: Baumann KI, Moll I, Halata Z, eds. The Merkel Cell – Structure – Development – Function – and Cancerogenesis. Berlin, Heidelberg, New York, Tokyo: Springer-Verlag, pp. 219–222.
Haass NK, Houdek P, Wladykowski E, Moll I, Brandner JM (2003b) Expression patterns of tight junction proteins in Merkel cell carcinoma. In: Baumann KI, Moll I, Halata Z, eds. The Merkel Cell – Structure – Development – Function – and Cancerogenesis. Berlin, Heidelberg, New York, Tokyo: Springer-Verlag, pp. 223–226.
Haegel H, Larue L, Ohsugi M, Fedorov L, Herrenknecht K, Kemler R (1995) Lack of β-catenin affects mouse development at gastrulation. Development 121: 3529–3537.
Hajra KM, Fearon ER (2002) Cadherin and catenin alterations in human cancer. Genes Chromosomes Cancer 34: 255–268.
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70.
Hendrix MJ, Seftor EA, Meltzer PS, Gardner LM, Hess AR, Kirschmann DA, Schatteman GC, Seftor RE (2001) Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry. Proc Natl Acad Sci USA 98: 8018–8023.
Hendrix MJ, Seftor EA, Hess AR, Seftor RE (2003) Molecular plasticity of human melanoma cells. Oncogene 22: 3070–3075.
Hess AR, Seftor EA, Gardner LM, Carles-Kinch K, Schneider GB, Seftor RE, Kinch MS, Hendrix MJ (2001) Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation: Role of epithelial cell kinase (Eck/EphA2). Cancer Res 61: 3250–3255.
Hirai Y, Nose A, Kobayashi S, Takeichi M (1989a) Expression and role of E-and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis. Development 105: 263–270
Hirai Y, Nose A, Kobayashi S, Takeichi M (1989b) Expression and role of E-and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis. Development 105: 271–277.
Hirano S, Nose A, Hatta K, Kawakami A, Takeichi M (1987) Calcium-dependent cell–cell adhesion molecules (cadherins): Subclass speci-ficities and possible involvement of actin bundles. J Cell Biol 105: 2501–2510.
Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153: 333–339.
Hirschi KK, Xu CE, Tsukamoto T, Sager R (1996) Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential. Cell Growth Diff 7: 861–870.
Hoschuetzky H, Aberle H, Kemler R (1994) Beta-catenin mediates the interaction of the cadherin–catenin complex with epidermal growth factor receptor. J Cell Biol 127: 1375–1380.
Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ (2001) Coordinately up-regulated genes in ovarian cancer. Cancer Res 61: 3869–3876.
Hsu MY, Wheelock MJ, Johnson KR, Herlyn M (1996) Shifts in cadherin profiles between human normal melanocytes and melanomas. J Investig Dermatol Symp Proc 1: 188–194.
Hsu MY, Andl T, Li G, Meinkoth JL, Herlyn M (2000a) Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression J Cell Sci 113: 1535–1542.
Hsu MY, Meier FE, Nesbit M, Hsu JY, Van Belle P, Elder DE, Herlyn M (2000b) E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol 156: 1515–1525.
Huang RP, Fan Y, Hossain MZ, Peng A, Zeng ZL, Boynton AL (1998) Reversion of the neoplastic phenotype of human glioblastoma cells by connexin 43 (cx 43). Cancer Res 58: 5089–5096.
Huang RP, Hossain MZ, Sehgal A, Boynton AL (1999) Reduced connexin43 expression in high-grade human brain glioma cells. J Surg Oncol 70: 21–24.
Hülsken J, Birchmeier W, Behrens J (1994) E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J Cell Biol 127: 2061–2069.
Ito A, Katoh F, Kataoka TR, Okada M, Tsubota N, Asada H, Yoshikawa K, Maeda S, Kitamura Y, Yamasaki H, Nojima H (2000) A role for heterologous gap junctions between melanoma and endothelial cells in metastasis. J Clin Invest 105: 1189–1197.
Jamal S, Schneider RJ (2002) UV-induction of keratinocyte endothelin-1 downregulates E cadherin in melanocytes and melanoma cells. J Clin Invest 110: 443–452.
Jiang JX, Goodenough DA (1996) Heteromeric connexons in lens gap junction channels. Proc Natl Acad Sci USA 93: 1287–1291.
Jinn Y, Ichioka M, Marumo F (1998) Expression of connexin32 and connexin43 gap junction proteins and E-cadherin in human lung cancer. Cancer Lett 127: 161–169.
Kaibuchi K, Kuroda S, Fukata M, Nakagawa M (1999) Regulation of cadherin-mediated cell–cell adhesion by the Rho family GTPases. Curr Opin Cell Biol 11: 591–596.
Kerjaschki D, Krisch K, Sleyter UB, Umrath W, Jakesz R, Depisch D, Kokoschka R, Horandner H (1979) The structure of tight junctions in human thyroid tumors. A systematic freeze-fracture study. Am J Pathol 96: 207–225.
Kimura Y, Shiozaki H, Hirao M, Maeno Y, Doki Y, Inoue M, Monden T, Ando-Akatsuka Y, Furuse M, Tsukita S, Monden M(1997) Expression of occludin, tight-junction-associated protein, in human digestive tract. Am J Pathol 151: 45–54.
King TJ, Fukushima LH, Hieber AD, Shimabukuro KA, Sakr WA, Bertram JS (2000) Reduced levels of connexin43 in cervical dysplasia: Inducible expression in a cervical carcinoma cell line decreases neoplastic potential with implications for tumor progression. Carcinogenesis 21: 1097–1109.
Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S (2003) Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene 22: 2021–2033.
Kramer F, White K, Kubbies M, Swisshelm K, Weber BH (2000) Genomic organization of claudin-1 and its assessment in hereditary and sporadic breast cancer. Hum Genet 107: 249–256.
Krutovskikh V, Mazzoleni G, Mironov N, Omori Y, Aguelon AM, Mesnil M, Berger F, Partensky C, Yamasaki H (1994) Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32. Int J Cancer 56: 87–94.
Krutovskikh VA, Yamasaki H, Tsuda H, Asamoto M(1998) Inhibition of intrinsic gap-junction intercellular communication and enhancement of tumorigenicity of the rat bladder carcinoma cell line BC31 by a dominant-negative connexin 43 mutant. Mol Carcinogen 23: 254–261.
Krutovskikh VA, Troyanovsky SM, Piccoli C, Tsuda H, Asamoto M, Yamasaki H (2000) Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo. Oncogene 19: 505–513.
Krutovskikh VA, Piccoli C, Yamasaki H, Yamasaki H (2002) Gap junction intercellular communication propagates cell death in cancerous cells. Oncogene 21: 1989–1999.
Langbein L, Grund C, Kuhn C, Praetzel S, Kartenbeck J, Brandner JM, Moll I, Franke WW(2002) Tight junctions and compositionally related junctional structures in mammalian stratified epithelia and cell cultures derived there from. Eur J Cell Biol 81: 419–435.
Li D, Mrsny RJ (2000) Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin. J Cell Biol 148: 791–800.
Li G, Satyamoorthy K, Herlyn M (2001a) N-cadherin-mediated inter-cellular interactions promote survival and migration of melanoma cells. Cancer Res 61: 3819–3825.
Li G, Schaider H, Satyamoorthy K, Hanakawa Y, Hashimoto K, Herlyn M (2001b) Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene 20: 8125–8135.
Li G, Satayamoorthy K, Herlyn M (2002) Dynamics of cell interactions during melanoma development. Crit Rev Oral Biol Med 13: 62–70.
Li G, Satayamoorthy K, Meier F, Berking C, Bogenrieder T, Herlyn M (2003) Function and regulation of melanoma–stromal fibroblast inter-actions: When seed meets soil. Oncogene 22: 3162–3171.
Loewenstein WR (1981) Junctional intercellular communication: The cell-to-cell membrane channel. Physiol Rev 61: 829–913.
Long H, Crean CD, Lee WH, Cummings OW, Gabig TG (2001) Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res 61: 7878–7881.
Martin TA, Jiang WG (2001) Tight junctions and their role in cancer metastasis. Histol Histopathol 16: 1183–1195.
Meyer CG, Amedofu GK, Brandner JM, Pohland D, Timmann C, Horstmann RD (2002) Selection for deafness? Nat Med 8: 1332–1333.
McGary EC, Lev DC, Bar-Eli M (2002) Cellular adhesion pathways and metastatic potential of human melanoma. Cancer Biol Ther 1: 459–465.
Mitic LL, Anderson JM (1998) Molecular architecture of tight junctions. Annu Rev Physiol 60: 121–142.
Miwa N, Furuse M, Tsukita S, Niikawa N, Nakamura Y, Furukawa Y (2001) Involvement of claudin-1 in the β-catenin/Tcf signaling path-way and its frequent upregulation in human colorectal cancers. Oncol Res 12: 469–476.
Moennikes O, Buchmann A, Willecke K, Traub O, Schwarz M (2000) Hepatocarcinogenesis in female mice with mosaic expression of connexin32. Hepatology 32: 501–506.
Mullin JM (1997) Potential interplay between luminal growth factors and increased tight junction permeability in epithelial carcinogenesis. J Exp Zool 279: 484–489.
Nacht M, Ferguson AT, Zhang W, Petroziello JM, Cook BP, Gao YH, Maguire S, Riley D, Coppola G, Landes GM, Madden SL, Sukumar S (1999) Combining serial analysis of gene expression and array technologies to identify genes differentially expressed in breast cancer. Cancer Res 59: 5464–5470.
Naus CC (2002) Gap junctions and tumour progression. Can J Physiol Pharmacol 80: 136–141.
Nishimura EK, Yoshida H, Kunisada T, Nishikawa SI (1999) Regulation of E-and P-cadherin expression correlated with melanocyte migration and diversification. Dev Biol 215: 155–166.
Omori Y, Yamasaki H (1998) Mutated connexin 43 proteins inhibit rat glioma cell growth suppression mediated by wild-type connexin 43 in a dominant-negative manner. Int J Cancer 78: 446–453.
Park CC, Bissell MJ, Barcellos-Hoff MH (2000) The influence of the microenvironment on the malignant phenotype. Mol Med Today 6: 324–329.
Pitts JD, Finbow ME, Kam E (1988) Junctional communication and cellular differentiation. Br J Cancer 9(Suppl.): 52–57.
Poser I, Dominguez D, de Herreros AG, Varnai A, Buettner R, Bosserhoff AK (2001) Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem 276: 24661–24666.
Pummi K, Malminen M, Aho H, Karvonen SL, Peltonen J, Peltonen S (2001) Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes. J Invest Dermatol 117: 1050–1058.
Rangel LB, Agarwal R, D'souza T, Pizer ES, Alo PL, Lancaster WD, Gregoire L, Schwartz DR, Cho KR, Morin PJ (2003) Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. Clin Cancer Res 9: 2567–2675.
Ren J, Hamada J, Takeichi N, Fujikawa S, Kobayashi H(1990) Ultrastructural differences in junctional intercellular communication between highly and weakly metastatic clones derived from rat mammary carcinoma. Cancer Res 50: 358–362.
Reynolds AB, Herbert L, Cleveland JL, Berg ST, Gaut JR (1992) p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors β-catenin, plakoglobin and armadillo. Oncogene 7: 2439–2445.
Richard G (2000) Connexins: A connection with the skin. Exp Dermatol 9: 77–96.
Salomon D, Masgrau E, Vischer S, Chanson M, Saurat JH, Spray DS, Meda P (1993) Gap junction proteins and communication in human epidermis. Prog Cell Res 3: 255–231.
Sanders DS, Blessing K, Hassan GA, Bruton R, Marsden JR, Jankowski J (1999) Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. Mol Pathol 52: 151–157.
Satyamoorthy K, Muyrers J, Meier F, Patel D, Herlyn M (2001) Mel-CAM-specific genetic suppressor elements inhibit melanoma growth through loss of gap junctional communication. Oncogene 20: 4676–4684.
Saunders MM, Seraj MJ, Li Z, Zhou Z, Winter CR, Welch DR, Donahue HJ (2001) Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication. Cancer Res 61: 1765–1767.
Schmidt A, Heid HW, Schafer S, Nuber UA, Zimbelmann R, Franke WW (1994) Desmosomes and cytoskeletal architecture in epithelial differentiation: Cell type-specific plaque components and intermediate filament anchorage. Eur J Cell Biol 65: 229–245.
Seftor RE, Seftor EA, Koshikawa N, Meltzer PS, Gardner LM, Bilban M, Stetler-Stevenson WG, Quaranta V, Hendrix MJ (2001) Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 61: 6322–6327.
Seiberg M, Paine C, Sharlow E, Andrade-Gordon P, Costanzo M, Eisinger M, Shapiro SS (2000) The protease-activated receptor 2 regulates pigmentation via keratinocyte–melanocyte interactions. Exp Cell Res 254: 25–32.
Seline PC, Norris DA, Horikawa T, Fujita M, Middleton MH, Morelli JG (1996) Expression of E and P-cadherin by melanoma cells decreases in progressive melanomas and following ultraviolet radiation. J Invest Dermatol 106: 1320–1324.
Shapiro L, Fannon AM, Kwong PD, Thompson A, Lehmann MS, Grubel G, Legrand JF, Als-Nielsen J, Colman DR, Hendrickson WA (1995) Structural basis of cell–cell adhesion by cadherins. Nature 374: 327–337.
Sharpe C, Lawrence N, Martinez Arias A (2001) Wnt signalling: Atheme with nuclear variations. Bioessays 23: 311–318.
Shih IM, Elder DE, Hsu MY, Herlyn M (1994) Regulation of Mel-CAM/MUC18 expression on melanocytes of different stages of tumor progression by normal keratinocytes. AmJ Pathol 145: 837–845.
Silye R, Karayiannakis AJ, Syrigos KN, Poole S, van Noorden S, Batchelor W, Regele H, Sega W, Boesmueller H, Krausz T, Pignatelli M(1998) E-cadherin/catenin complex in benign and malignant melanocytic lesions. J Pathol 186: 350–355.
Smalley KSM (2003) A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? Int J Cancer 104: 527–532.
Soler AP, Miller RD, Laughlin KV, Carp NZ, Klurfeld DM, Mullin JM (1999) Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis 20: 1425–1431.
Soler C, Rousselle P, Damour O (1998) Cadherin mediated cell–cell adhesion is regulated by tyrosine phosphatases in human keratinocytes. Cell Adhes Commun 5: 13.
Spray DC (1994) Physiological and pharmacological regulation of gap junction channels. In: Citi S, ed. Molecular Mechanisms of Epithelial Cell Junctions: From Development to Disease. Austin, Texas: R.G. Landes Company, pp. 195–215.
Stauffer KA(1995) The gap junction proteins β1-connexin (connexin-32) and β2-connexin (connexin-26) can form heteromeric hemichannels. J Biol Chem 270: 6768–6772.
Stevenson BR, Keon BH (1998) The tight junction: Morphology to molecules. Annu Rev Cell Dev Biol 14: 89–109.
Su YA, Bittner ML, Chen Y, Tao L, Jiang Y, Zhang Y, Stephan DA, Trent JM (2000) Identification of tumor-suppressor genes using human melanoma cell lines UACC903, UACC903(+6), and SRS3 by comparison of expression profiles. Mol Carcinog 28: 119–127.
Suzuki ST (1996a) Structural and functional diversity of cadherin super-family: Are new members of cadherin superfamily involved in signal transduction pathway? J Cell Biochem 61: 531–542.
Suzuki ST (1996b) Protocadherins and diversity of the cadherin super-family. J Cell Sci 109: 2609–2611.
Tada J, Hashimoto K(1997) Ultrastructural localization of gap junctional protein connexin 43 in normal human skin, basal cell carcinoma and squamous cell carcinoma. J Cut Pathol 24: 628–635.
Takeichi M(1988) The cadherins: Cell–cell adhesion molecules controlling animal morphogenesis. Development 102: 639–655.
Tang A, Eller MS, Hara M, Yaar M, Hirohashi S, Gilchrest BA (1994) E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro. J Cell Sci 107: 983–992.
Temme A, Buchmann A, Gabriel HD, Nelles E, Schwarz M, Willecke K (1997) High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin32. Curr Biol 7: 713–716.
Tsai H, Werber J, Davia MO, Edelman M, Tanaka KE, Melman A, Christ GJ, Geliebter J (1996) Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells. Biochem Biophys Res Commun 227: 64–69.
Tselepis C, Chidgey M, North A, Garrod D(1998) Desmosomal adhesion inhibits invasive behavior. Proc Natl Acad Sci USA 95: 8064–8069.
Tsukita S, Furuse M, Itoh M (2001) Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2: 285–293.
Uchida Y, Matsuda K, Sasahara K, Kawabata H, Nishioka M (1995) Immunohistochemistry of gap junctions in normal and diseased gastric mucosa of humans. Gastroenterology 109: 1492–1496.
Veenstra RD (1996) Size and selectivity of gap junction channels formed from different connexins. J Bioenerg Biomembr 28: 326–337.
Weinstein RS, Merk FB, Alroy J (1976) The structure and function of intercellular junctions in cancer. Adv Cancer Res 23: 23–89.
Whittock NV, Bower C (2003) Genetic evidence for a novel human desmosomal cadherin, desmoglein 4. J Invest Dermatol 120: 523–530.
Wilgenbus KK, Kirkpatrick CJ, Knuechel R, Willecke K, Traub O(1992) Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int J Cancer 51: 522–529.
Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, Deutsch U, Sohl G (2002) Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 383: 725–737.
Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B (2003) Localization of claudin-3 in tight junctions of the blood–brain barrier is selectively lost during experimental auto-immune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 105: 586–592.
Yamaoka K, Nouchi T, Tazawa J, Hiranuma S, Marumo F, Sato C (1995) Expression of gap junction protein connexin 32 and E-cadherin in human hepatocellular carcinoma. J Hepatol 22: 536–539
Yamasaki H, Krutovskikh V, Mesnil M, Tanaka T, Zaidan-Dagli ML, Omori Y (1999) Role of connexin (gap junction) genes in cell growth control and carcinogenesis. CR Acad Sci III 322: 151–159.
Yap AS, Brieher WM, Gumbiner BM (1997) Molecular and functional analysis of cadherin-based adherens junctions. Ann Rev Cell Dev Biol 13: 119–146.
Zhang ZQ, Zhang W, Wang NQ, Bani-Yaghoub M, Lin ZX, Naus CC (1998) Suppression of tumorigenicity of human lung carcinoma cells after transfection with connexin43. Carcinogenesis 19: 1889–1894.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haass, N.K., Smalley, K.S. & Herlyn, M. The Role of Altered Cell–Cell Communication in Melanoma Progression. Histochem J 35, 309–318 (2004). https://doi.org/10.1023/B:HIJO.0000032362.35354.bb
Issue Date:
DOI: https://doi.org/10.1023/B:HIJO.0000032362.35354.bb