• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Oct 1996; 149(4): 1341–1349.
PMCID: PMC1865207

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

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Wingo PA, Tong T, Bolden S. Cancer statistics, 1995. CA Cancer J Clin. 1995 Jan-Feb;45(1):8–30. [PubMed]
  • Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J, Kleinman H, Martin GR, Meneguzzi G, Paulsson M, Sanes J, et al. A new nomenclature for the laminins. Matrix Biol. 1994 Apr;14(3):209–211. [PubMed]
  • Rousselle P, Lunstrum GP, Keene DR, Burgeson RE. Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol. 1991 Aug;114(3):567–576. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Marinkovich MP, Lunstrum GP, Burgeson RE. 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]
  • Timpl R. Structure and biological activity of basement membrane proteins. Eur J Biochem. 1989 Apr 1;180(3):487–502. [PubMed]
  • Vailly J, Verrando P, Champliaud MF, Gerecke D, Wagman DW, Baudoin C, Aberdam D, Burgeson R, Bauer E, Ortonne JP. The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant. Eur J Biochem. 1994 Jan 15;219(1-2):209–218. [PubMed]
  • Domloge-Hultsch N, Gammon WR, Briggaman RA, Gil SG, Carter WG, Yancey KB. 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. [PMC free article] [PubMed]
  • Carter WG, Ryan MC, Gahr PJ. Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Cell. 1991 May 17;65(4):599–610. [PubMed]
  • Aberdam D, Galliano MF, Vailly J, Pulkkinen L, Bonifas J, Christiano AM, Tryggvason K, Uitto J, Epstein EH, Jr, Ortonne JP, et al. 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. [PubMed]
  • Pyke C, Rømer J, Kallunki P, Lund LR, 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]
  • Vailly J, Szepetowski P, Mattei MG, Pedeutour F, Burgeson R, Ortonne JP, 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. [PubMed]
  • Yurchenco PD, Cheng YS, Colognato H. Laminin forms an independent network in basement membranes. J Cell Biol. 1992 Jun;117(5):1119–1133. [PMC free article] [PubMed]
  • Pulkkinen L, Gerecke DR, Christiano AM, Wagman DW, Burgeson RE, 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. [PubMed]
  • Nagle RB, Hao J, Knox JD, Dalkin BL, Clark V, Cress AE. 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]
  • Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990 Dec 20;348(6303):699–704. [PubMed]
  • Slawin KM, Ohori M, Dillioglugil O, Scardino PT. Screening for prostate cancer: an analysis of the early experience. CA Cancer J Clin. 1995 May-Jun;45(3):134–147. [PubMed]
  • Matsui C, Wang CK, Nelson CF, Bauer EA, Hoeffler WK. The assembly of laminin-5 subunits. J Biol Chem. 1995 Oct 6;270(40):23496–23503. [PubMed]
  • Yancey KB. Adhesion molecules. II: Interactions of keratinocytes with epidermal basement membrane. J Invest Dermatol. 1995 Jun;104(6):1008–1014. [PubMed]
  • Kallunki P, Sainio K, Eddy R, Byers M, Kallunki T, Sariola H, Beck K, Hirvonen H, Shows TB, 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. [PMC free article] [PubMed]
  • Pulkkinen L, Christiano AM, 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. [PubMed]
  • Vailly J, Pulkkinen L, Christiano AM, Tryggvason K, Uitto J, Ortonne JP, 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. [PubMed]
  • 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]
  • McGrath JA, Pulkkinen L, Christiano AM, Leigh IM, Eady RA, 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. [PubMed]
  • Dalton SL, Marcantonio EE, Assoian RK. 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]
  • Nagle RB, Knox JD, Wolf C, Bowden GT, Cress AE. Adhesion molecules, extracellular matrix, and proteases in prostate carcinoma. J Cell Biochem Suppl. 1994;19:232–237. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...