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Localization of laminin α3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers

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Abstract

The basement membrane (BM) proteins laminins, which consist of α, β and γ chains, play critical roles in the maintenance of tissue structures. One of laminin α chains, α3 has two isoforms, the truncated form α3A and the full-sized form α3B. In contrast to α3A laminins, little is known about α3B laminins. To show the histological distribution of the laminin α3B chain, we prepared α3B-specific monoclonal antibodies. Immunohistochemical analysis showed that the α3B chain was colocalized with the α3A, β3 and γ2 chains in the epithelial BMs of the skin, esophagus, breast and lung, suggesting the presence of laminin-3B32 (laminin-5B) and laminin-3A32 (laminin-5A). In the lung alveoli, laminin-3B32 was dominant over laminin-3A32, but vice versa in other epithelial BMs. In contrast, the BMs of blood vessels including capillaries were strongly positive for α3B, but almost or completely negative for α3A, β3 and γ2. α3B was colocalized with β1 and γ1 in these BMs. The α3B chain was scarcely detected in the vessels of malignant skin cancers, though the γ2 and β3 chains were highly expressed in the cancer cells. These results strongly suggest that the laminin α3B chain is widely expressed in vascular BMs of normal tissues, probably as laminin-3B11/3B21 (laminin-6B/7B).

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Abbreviations

BM:

Basement membrane

ECM:

Extracellular matrix

Lmxyz:

Laminin-xyz

mAb:

Monoclonal antibody

References

  • Abrass CK, Berfield AK, Ryan MC, Carter WG, Hansen KM (2006) Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene. Kidney Int 70:1062–1071. doi:10.1038/sj.ki.5001706

    Article  PubMed  CAS  Google Scholar 

  • Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P et al (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332. doi:10.1016/j.matbio.2005.05.006

    Article  PubMed  CAS  Google Scholar 

  • Baker SE, Hopkinson SB, Fitchmun M, Andreason GL, Frasier F, Plopper G et al (1996) Laminin-5 and hemidesmosomes: role of the alpha3 chain subunit in hemidesmosome stability and assembly. J Cell Sci 109:2509–2520

    PubMed  CAS  Google Scholar 

  • Carter WG, Ryan MC, Gahr PJ (1991) Epiligrin, a new cell adhesion ligand for integrin alpha3 beta1 in epithelial basement membranes. Cell 65:599–610. doi:10.1016/0092-8674(91)90092-D

    Article  PubMed  CAS  Google Scholar 

  • Champliaud MF, Lunstrum GP, Rousselle P, Nishiyama T, Keene DR, Burgeson RE (1996) Human amnion contains a novel laminin variant, laminin 7, which like laminin 6, covalently associates with laminin 5 to promote stable epithelial-stromal attachment. J Cell Biol 132:1189–1198. doi:10.1083/jcb.132.6.1189

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y-S, Champliaud M-F, Burgeson RE, Marinkovich MP, Yurchenco PD (1997) Self-assembly of laminin isoforms. J Biol Chem 272:31525–31532. doi:10.1074/jbc.272.50.31525

    Article  PubMed  CAS  Google Scholar 

  • Colognato H, Yurchenco PD (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218:213–234. doi :10.1002/(SICI)1097-0177(200006)218:2<213::AID-DVDY1>3.0.CO;2-R

  • Doliana R, Bellina I, Bucciotti F, Mongiat M, Perris R, Colombatti A (1997) The human alpha3b is a ‘full-sized’ laminin chain variant with a more widespread tissue expression than the truncated alpha3a. FEBS Lett 417:65–70. doi:10.1016/S0014-5793(97)01251-9

    Article  PubMed  CAS  Google Scholar 

  • Ferrigno O, Virolle T, Galliano MF, Chauvin N, Ortonne JP, Meneguzzi G et al (1997) Murine laminin alpha3A and alpha3B isoform chains are generated by usage of two promoters and alternative splicing. J Biol Chem 272:20502–20507. doi:10.1074/jbc.272.33.20502

    Article  PubMed  CAS  Google Scholar 

  • Fujita M, Khazenzon NM, Bose S, Sekiguchi K, Sasaki T, Carter WG et al (2005) Overexpression of beta1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases. Breast Cancer Res 7:R411–R421. doi:10.1186/bcr1011

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara H, Kikkawa Y, Sanzen N, Sekiguchi K (2001) Purification and characterization of human laminin-8. Laminin-8 stimulates cell adhesion and migration through alpha3beta1 and alpha6beta1 integrins. J Biol Chem 276:17550–17558. doi:10.1074/jbc.M010155200

    Article  PubMed  CAS  Google Scholar 

  • Galliano MF, Aberdam D, Aguzzi A, Ortonne JP, Meneguzzi G (1995) Cloning and complete primary structure of the mouse laminin alpha 3 chain. Distinct expression pattern of the laminin alpha 3A and alpha 3B chain isoforms. J Biol Chem 270:21820–21826. doi:10.1074/jbc.270.37.21820

    Article  PubMed  CAS  Google Scholar 

  • Garbe JH, Gohring W, Mann K, Timpl R, Sasaki T (2002) Complete sequence, recombinant analysis and binding to laminins and sulphated ligands of the N-terminal domains of laminin alpha3B and alpha5 chains. Biochem J 362:213–221. doi:10.1042/0264-6021:3620213

    Article  PubMed  CAS  Google Scholar 

  • Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM (2005) Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 85:979–1000. doi:10.1152/physrev.00014.2004

    Article  PubMed  CAS  Google Scholar 

  • Hirosaki T, Mizushima H, Tsubota Y, Moriyama K, Miyazaki K (2000) Structural requirement of carboxyl-terminal globular domains of laminin alpha3 chain for promotion of rapid cell adhesion and migration by laminin-5. J Biol Chem 275:22495–22502. doi:10.1074/jbc.M001326200

    Article  PubMed  CAS  Google Scholar 

  • Hirosaki T, Tsubota Y, Kariya Y, Moriyama K, Mizushima H, Miyazaki K (2002) Laminin-6 is activated by proteolytic processing and regulates cellular adhesion and migration differently from laminin-5. J Biol Chem 277:49287–49295. doi:10.1074/jbc.M111096200

    Article  PubMed  CAS  Google Scholar 

  • Kariya Y, Ishida K, Tsubota Y, Nakashima Y, Hirosaki T, Ogawa T et al (2002) Efficient expression system of human recombinant laminin-5. J Biochem 132:607–612

    PubMed  CAS  Google Scholar 

  • Kariya Y, Tsubota Y, Hirosaki T, Mizushima H, Puzon-McLaughlin W, Takada Y et al (2003) Differential regulation of cellular adhesion and migration by recombinant laminin-5 forms with partial deletion or mutation within the G3 domain of alpha3 chain. J Cell Biochem 88:506–520. doi:10.1002/jcb.10350

    Article  PubMed  CAS  Google Scholar 

  • Kariya Y, Yasuda C, Nakashima Y, Ishida K, Tsubota Y, Miyazaki K (2004) Characterization of laminin 5B and NH2-terminal proteolytic fragment of its alpha3B chain: promotion of cellular adhesion, migration, and proliferation. J Biol Chem 279:24774–24784. doi:10.1074/jbc.M400670200

    Article  PubMed  CAS  Google Scholar 

  • Kikkawa Y, Sanzen N, Sekiguchi K (1998) Isolation and characterization of laminin-10/11 secreted by human lung carcinoma cells. laminin-10/11 mediates cell adhesion through integrin alpha3 beta1. J Biol Chem 273:15854–15859. doi:10.1074/jbc.273.25.15854

    Article  PubMed  CAS  Google Scholar 

  • Kivirikko S, McGrath JA, Baudoin C, Aberdam D, Ciatti S, Dunnill MG et al (1995) A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa. Hum Mol Genet 4:959–962. doi:10.1093/hmg/4.5.959

    Article  PubMed  CAS  Google Scholar 

  • Koshikawa N, Moriyama K, Takamura H, Mizushima H, Nagashima Y, Yanoma S et al (1999) Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells. Cancer Res 59:5596–5601

    PubMed  CAS  Google Scholar 

  • Li J, Zhou L, Tran HT, Chen Y, Nguyen NE, Karasek MA et al (2006) Overexpression of laminin-8 in human dermal microvascular endothelial cells promotes angiogenesis-related functions. J Invest Dermatol 126:432–440. doi:10.1038/sj.jid.5700089

    Article  PubMed  CAS  Google Scholar 

  • Määttä M, Virtanen I, Burgeson R, Autio-Harmainen H (2001) Comparative analysis of the distribution of laminin chains in the basement membranes in some malignant epithelial tumors: the alpha1 chain of laminin shows a selected expression pattern in human carcinomas. J Histochem Cytochem 49:711–726

    PubMed  Google Scholar 

  • Marinkovich MP, Lunstrum GP, Keene DR, Burgeson RE (1992) The dermal-epidermal junction of human skin contains a novel laminin variant. J Cell Biol 119:695–703. doi:10.1083/jcb.119.3.695

    Article  PubMed  CAS  Google Scholar 

  • Miner JH, Patton BL, Lentz SI, Gilbert DJ, Snider WD, Jenkins NA et al (1997) The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha3 isoform. J Cell Biol 137:685–701. doi:10.1083/jcb.137.3.685

    Article  PubMed  CAS  Google Scholar 

  • Miyazaki K (2006) Laminin-5 (laminin-332): unique biological activity and role in tumor growth and invasion. Cancer Sci 97:91–98. doi:10.1111/j.1349-7006.2006.00150.x

    Article  PubMed  CAS  Google Scholar 

  • Mizushima H, Miyagi Y, Kikkawa Y, Yamanaka N, Yasumitsu H, Misugi K et al (1996) Differential expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promoter and growth factors. J Biochem 120:1196–1202

    PubMed  CAS  Google Scholar 

  • Mizushima H, Koshikawa N, Moriyama K, Takamura H, Nagashima Y, Hirahara F et al (1998) Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues. Horm Res 50:7–14. doi:10.1159/000053118

    Article  PubMed  CAS  Google Scholar 

  • Nakashima Y, Kariya Y, Yasuda C, Miyazaki K (2005) Regulation of cell adhesion and type VII collagen binding by beta3 chain short arm of laminin-5: effect of its proteolytic cleavage. J Biochem 138:539–552. doi:10.1093/jb/mvi153

    Article  PubMed  CAS  Google Scholar 

  • Nakashima Y, Kariya Y, Miyazaki K (2007) The β3 chain short arm of laminin-332 (laminin-5) induces matrix assembly and cell adhesion activity of laminin-511 (laminin-10). J Cell Biochem 100:545–556. doi:10.1002/jcb.21032

    Article  PubMed  CAS  Google Scholar 

  • Nielsen PK, Yamada Y (2001) Identification of cell-binding sites on the Laminin alpha 5 N-terminal domain by site-directed mutagenesis. J Biol Chem 276:10906–10912. doi:10.1074/jbc.M008743200

    Article  PubMed  CAS  Google Scholar 

  • Ono Y, Nakanishi Y, Ino Y, Niki T, Yamada T, Yoshimura K et al (1999) Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. Cancer 85:2315–2321. doi :10.1002/(SICI)1097-0142(19990601)85:11<2315::AID-CNCR3>3.0.CO;2-Y

  • Pyke C, Salo S, Ralfkiaer E, Romer J, Danø K, Tryggvason K (1995) Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 55:4132–4139

    PubMed  CAS  Google Scholar 

  • Rousselle P, Lunstrum GP, Keene DR, Bureson RE (1991) Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol 114:567–576. doi:10.1083/jcb.114.3.567

    Article  PubMed  CAS  Google Scholar 

  • Ryan MC, Tizard R, VanDevanter DR, Carter WG (1994) Cloning of the LamA3 gene encoding the alpha3 chain of the adhesive ligand epiligrin. Expression in wound repair. J Biol Chem 269:22779–22787

    PubMed  CAS  Google Scholar 

  • Zhou Z, Doi M, Wang J, Cao R, Liu B, Chan KM et al (2004) Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice. Cancer Res 64:4059–4063. doi:10.1158/0008-5472.CAN-04-0291

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Ms. Naoko Kato for technical support. We are grateful to Drs. S. Higashi and K. Yamamoto for helpful discussions. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Kaoru Miyazaki.

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Kariya, Y., Mori, T., Yasuda, C. et al. Localization of laminin α3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers. J Mol Hist 39, 435–446 (2008). https://doi.org/10.1007/s10735-008-9183-0

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