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. 1996 Oct;149(4):1341–1349.

Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant and normal prostate.

J Hao 1, Y Yang 1, K M McDaniel 1, B L Dalkin 1, A E Cress 1, R B Nagle 1
PMCID: PMC1865207  PMID: 8863681

Abstract

Laminin 5 is an extracellular matrix protein integral to the formation of the hemidesmosomes that attach normal basal cells to the underlying basal lamina. We have shown that these hemidesmosomal complexes are lost in prostate carcinoma, possibly allowing malignant cells to detach from the anchoring structures and then to invade and migrate through the adjacent tissue. Our previous immunohistochemical studies of normal and malignant human prostate tissue demonstrated that the laminin subchains alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 were all expressed as normal components of the basal lamina surrounding prostate glands. Although most of these subchains were also expressed by the de novo basal lamina synthesized by prostate carcinoma, the gamma 2 subchain of laminin 5 was not detected. In an effort to investigate the role laminin 5 plays in the tumorigenesis of prostate carcinoma, the protein expression of the three subchains of laminin 5 (alpha 3, beta 3, and gamma 2) was compared in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma using immunohistochemistry. The results showed that the protein for the alpha 3 subchain of laminin 5 is retained by both normal prostate epithelium and prostate carcinoma, but the beta 3 and the gamma 2 subchains were not detected in invasive carcinoma. Despite the absence of the gamma 2 protein, however, the carcinoma cells continued to express substantial amounts of the gamma 2 mRNA. Although it is unclear how the gene for the gamma 2 subchain of laminin 5 is regulated, results of this study suggest that there is a post-transcriptional defect in the expression of the gamma 2 subchain that occurs during the progression from a premalignant lesion to invasive carcinoma. As laminin 5 is a component of the anchoring filaments, the failure to express the gamma 2 subchain may contribute to the failure to form anchoring filaments and hemidesmosomes. This failure of hemidesmosome formation results in a less stable epithelial-stromal junction, which may allow malignant cells more potential to invade and spread through adjacent structures.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aberdam D., Galliano M. F., Vailly J., Pulkkinen L., Bonifas J., Christiano A. M., Tryggvason K., Uitto J., Epstein E. H., Jr, Ortonne J. P. Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5). Nat Genet. 1994 Mar;6(3):299–304. doi: 10.1038/ng0394-299. [DOI] [PubMed] [Google Scholar]
  2. Basset P., Bellocq J. P., Wolf C., Stoll I., Hutin P., Limacher J. M., Podhajcer O. L., Chenard M. P., Rio M. C., Chambon P. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990 Dec 20;348(6303):699–704. doi: 10.1038/348699a0. [DOI] [PubMed] [Google Scholar]
  3. Burgeson R. E., Chiquet M., Deutzmann R., Ekblom P., Engel J., Kleinman H., Martin G. R., Meneguzzi G., Paulsson M., Sanes J. A new nomenclature for the laminins. Matrix Biol. 1994 Apr;14(3):209–211. doi: 10.1016/0945-053x(94)90184-8. [DOI] [PubMed] [Google Scholar]
  4. Carter W. G., Ryan M. C., Gahr P. J. Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Cell. 1991 May 17;65(4):599–610. doi: 10.1016/0092-8674(91)90092-d. [DOI] [PubMed] [Google Scholar]
  5. Dalton S. L., Marcantonio E. E., Assoian R. K. Cell attachment controls fibronectin and alpha 5 beta 1 integrin levels in fibroblasts. Implications for anchorage-dependent and -independent growth. J Biol Chem. 1992 Apr 25;267(12):8186–8191. [PubMed] [Google Scholar]
  6. Domloge-Hultsch N., Gammon W. R., Briggaman R. A., Gil S. G., Carter W. G., Yancey K. B. Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease. J Clin Invest. 1992 Oct;90(4):1628–1633. doi: 10.1172/JCI116033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kallunki P., Sainio K., Eddy R., Byers M., Kallunki T., Sariola H., Beck K., Hirvonen H., Shows T. B., Tryggvason K. A truncated laminin chain homologous to the B2 chain: structure, spatial expression, and chromosomal assignment. J Cell Biol. 1992 Nov;119(3):679–693. doi: 10.1083/jcb.119.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Marinkovich M. P., Lunstrum G. P., Burgeson R. E. The anchoring filament protein kalinin is synthesized and secreted as a high molecular weight precursor. J Biol Chem. 1992 Sep 5;267(25):17900–17906. [PubMed] [Google Scholar]
  9. Matsui C., Wang C. K., Nelson C. F., Bauer E. A., Hoeffler W. K. The assembly of laminin-5 subunits. J Biol Chem. 1995 Oct 6;270(40):23496–23503. doi: 10.1074/jbc.270.40.23496. [DOI] [PubMed] [Google Scholar]
  10. McGrath J. A., Pulkkinen L., Christiano A. M., Leigh I. M., Eady R. A., Uitto J. Altered laminin 5 expression due to mutations in the gene encoding the beta 3 chain (LAMB3) in generalized atrophic benign epidermolysis bullosa. J Invest Dermatol. 1995 Apr;104(4):467–474. doi: 10.1111/1523-1747.ep12605904. [DOI] [PubMed] [Google Scholar]
  11. Nagle R. B., Hao J., Knox J. D., Dalkin B. L., Clark V., Cress A. E. Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue. Am J Pathol. 1995 Jun;146(6):1498–1507. [PMC free article] [PubMed] [Google Scholar]
  12. Nagle R. B., Knox J. D., Wolf C., Bowden G. T., Cress A. E. Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. J Cell Biochem Suppl. 1994;19:232–237. [PubMed] [Google Scholar]
  13. Pulkkinen L., Christiano A. M., Airenne T., Haakana H., Tryggvason K., Uitto J. Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet. 1994 Mar;6(3):293–297. doi: 10.1038/ng0394-293. [DOI] [PubMed] [Google Scholar]
  14. Pulkkinen L., Gerecke D. R., Christiano A. M., Wagman D. W., Burgeson R. E., Uitto J. Cloning of the beta 3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa. Genomics. 1995 Jan 1;25(1):192–198. doi: 10.1016/0888-7543(95)80125-6. [DOI] [PubMed] [Google Scholar]
  15. Pyke C., Rømer J., Kallunki P., Lund L. R., Ralfkiaer E., Danø K., Tryggvason K. The gamma 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers. Am J Pathol. 1994 Oct;145(4):782–791. [PMC free article] [PubMed] [Google Scholar]
  16. Pyke C., Salo S., Ralfkiaer E., Rømer J., Danø K., Tryggvason K. 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. 1995 Sep 15;55(18):4132–4139. [PubMed] [Google Scholar]
  17. Rousselle P., Aumailley M. Kalinin is more efficient than laminin in promoting adhesion of primary keratinocytes and some other epithelial cells and has a different requirement for integrin receptors. J Cell Biol. 1994 Apr;125(1):205–214. doi: 10.1083/jcb.125.1.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rousselle P., Lunstrum G. P., Keene D. R., Burgeson R. E. Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol. 1991 Aug;114(3):567–576. doi: 10.1083/jcb.114.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Slawin K. M., Ohori M., Dillioglugil O., Scardino P. T. Screening for prostate cancer: an analysis of the early experience. CA Cancer J Clin. 1995 May-Jun;45(3):134–147. doi: 10.3322/canjclin.45.3.134. [DOI] [PubMed] [Google Scholar]
  20. Timpl R. Structure and biological activity of basement membrane proteins. Eur J Biochem. 1989 Apr 1;180(3):487–502. doi: 10.1111/j.1432-1033.1989.tb14673.x. [DOI] [PubMed] [Google Scholar]
  21. Vailly J., Pulkkinen L., Christiano A. M., Tryggvason K., Uitto J., Ortonne J. P., Meneguzzi G. Identification of a homozygous exon-skipping mutation in the LAMC2 gene in a patient with Herlitz's junctional epidermolysis bullosa. J Invest Dermatol. 1995 Mar;104(3):434–437. doi: 10.1111/1523-1747.ep12666027. [DOI] [PubMed] [Google Scholar]
  22. Vailly J., Szepetowski P., Mattei M. G., Pedeutour F., Burgeson R., Ortonne J. P., Meneguzzi G. The genes for nicein/kalinin 125- and 100-kDa subunits, candidates for junctional epidermolysis bullosa, map to chromosomes 1q32 and 1q25-q31. Genomics. 1994 May 1;21(1):286–288. doi: 10.1006/geno.1994.1263. [DOI] [PubMed] [Google Scholar]
  23. Vailly J., Verrando P., Champliaud M. F., Gerecke D., Wagman D. W., Baudoin C., Aberdam D., Burgeson R., Bauer E., Ortonne J. P. The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant. Eur J Biochem. 1994 Jan 15;219(1-2):209–218. doi: 10.1111/j.1432-1033.1994.tb19932.x. [DOI] [PubMed] [Google Scholar]
  24. Wingo P. A., Tong T., Bolden S. Cancer statistics, 1995. CA Cancer J Clin. 1995 Jan-Feb;45(1):8–30. doi: 10.3322/canjclin.45.1.8. [DOI] [PubMed] [Google Scholar]
  25. Yancey K. B. Adhesion molecules. II: Interactions of keratinocytes with epidermal basement membrane. J Invest Dermatol. 1995 Jun;104(6):1008–1014. doi: 10.1111/1523-1747.ep12606244. [DOI] [PubMed] [Google Scholar]
  26. Yurchenco P. D., Cheng Y. S., Colognato H. Laminin forms an independent network in basement membranes. J Cell Biol. 1992 Jun;117(5):1119–1133. doi: 10.1083/jcb.117.5.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]

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