Home LiteratureArticle Details
PMID: 8780383 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alpha 6 beta 4 integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma. Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: implications for acquisition of the invading phenotype.

The American journal of pathology ·Vol. 149 ·No. 3 ·1996-09-00 ·Pages 781-93

Tani T, Karttunen T, Kiviluoto T, Kivilaakso E, Burgeson RE, Sipponen P, Virtanen I

Abstract

We studied the expression and distribution of different laminin chains, the alpha 6 beta 4 integrin and type VII collagen, i.e., components of the epithelial adhesion complex, in gastric carcinomas and in suggested preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha 6 beta 4 integrin, which is a receptor for both laminin-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastric epithelium showed a similar expression pattern of laminins and the alpha 6 beta 4 integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha 6 beta 4 integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma, and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta 4 integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma.

MeSH Terms
Antigens, Surface/biosynthesis Biomarkers, Tumor/biosynthesis Cell Adhesion/physiology Cell Adhesion Molecules/biosynthesis Collagen/biosynthesis Epithelium/chemistry Gastritis, Atrophic/pathology Humans Integrin alpha6beta4 Integrins/biosynthesis Intestinal Mucosa/metabolism Intestines/pathology Laminin/biosynthesis Metaplasia/metabolism,pathology Muscle, Smooth/pathology Neoplasm Invasiveness Phenotype Stomach/chemistry Stomach Neoplasms/pathology,physiopathology
Chemicals
Antigens, Surface Biomarkers, Tumor Cell Adhesion Molecules Integrin alpha6beta4 Integrins Laminin kalinin Collagen
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Tani T
Department of Anatomy, University of Helsinki, Finland.
Karttunen T
Kiviluoto T
Kivilaakso E
Burgeson R E
Sipponen P
Virtanen I
References (46)
46 references, click to expand
  1. Gastric carcinoma: failed adaptation to Helicobacter pylori.
    Scand J Gastroenterol Suppl. 1992;193:33-8 PMID: 1290056
  2. [3H]thymidine autoradiographic and alkaline phosphatase histochemical studies of intestinal metaplasia of the human stomach.
    Histochem J. 1983 Oct;15(10):953-9 PMID: 6643114
  3. Distribution patterns of type VII collagen in normal and malignant human tissues.
    Am J Pathol. 1991 Aug;139(2):451-9 PMID: 1867328
  4. Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments.
    J Cell Biol. 1991 Aug;114(3):567-76 PMID: 1860885
  5. CELL PROLIFERATION AND MIGRATION IN THE STOMACH, DUODENUM, AND RECTUM OF MAN: RADIOAUTOGRAPHIC STUDIES.
    Gastroenterology. 1964 Apr;46:405-17 PMID: 14141780
  6. Helicobacter pylori and gastric carcinogenesis.
    Am J Surg Pathol. 1995;19 Suppl 1:S37-43 PMID: 7762738
  7. Gastric carcinoma. A pathobiological classification.
    Cancer. 1977 Jun;39(6):2475-85 PMID: 872047
  8. Integrins and their accessory adhesion molecules in mammary carcinomas: loss of polarization in poorly differentiated tumors.
    Hum Pathol. 1992 Oct;23(10):1159-66 PMID: 1383121
  9. Tritiated thymidine autoradiographic study on histogenesis and spreading of intestinal metaplasia in human stomach.
    Pathol Res Pract. 1979 Jan;164(3):224-37 PMID: 461230
  10. THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION.
    Acta Pathol Microbiol Scand. 1965;64:31-49 PMID: 14320675
  11. 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):4132-9 PMID: 7664291
  12. Distribution of fibronectin and laminin in early and advanced signet-ring-cell carcinomas of the stomach.
    Int J Cancer. 1989 Feb 15;43(2):263-9 PMID: 2537263
  13. Tumor cell invasion, matrix metalloproteinases, and the dogma.
    Lab Invest. 1994 Jun;70(6):781-3 PMID: 8015282
  14. Basement membrane diversity detected by monoclonal antibodies.
    Differentiation. 1984;26(1):49-54 PMID: 6370774
  15. Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.
    J Cell Biol. 1990 Oct;111(4):1593-604 PMID: 1976638
  16. Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.
    Am J Pathol. 1994 Jul;145(1):167-74 PMID: 8030747
  17. Loss of alpha 6 and beta 4 integrin subunits coincides with loss of basement membrane components in oral squamous cell carcinomas.
    J Pathol. 1993 Nov;171(3):183-90 PMID: 8277367
  18. A function for the integrin alpha 6 beta 4 in the hemidesmosome.
    Cell Regul. 1991 Jun;2(6):427-38 PMID: 1883873
  19. Reciprocal expression of laminin A-chain isoforms along the crypt-villus axis in the human small intestine.
    Gastroenterology. 1994 Apr;106(4):829-39 PMID: 8143989
  20. Morphology of the basement membrane.
    Microsc Res Tech. 1994 Jun 1;28(2):95-124 PMID: 8054667
  21. Laminin receptors: achieving specificity through cooperation.
    Trends Cell Biol. 1995 Nov;5(11):419-23 PMID: 14732046
  22. Expression of laminin, collagen IV, fibronectin, and type IV collagenase in gastric carcinoma. An immunohistochemical study of 87 patients.
    Cancer. 1994 Feb 1;73(3):518-27 PMID: 8299074
  23. Heterotypic cellular cooperation in gut morphogenesis and differentiation.
    Semin Cell Biol. 1993 Jun;4(3):221-30 PMID: 8347838
  24. Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.
    J Cell Biol. 1994 Feb;124(3):381-94 PMID: 8294519
  25. Expression of cytokeratin No. 19 polypeptide in genital papillomavirus lesions.
    Gynecol Obstet Invest. 1990;29(1):59-66 PMID: 1693587
  26. The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression.
    Cancer Metastasis Rev. 1995 Sep;14(3):219-28 PMID: 8548870
  27. The role of basement membrane in colorectal cancer invasion and liver metastasis.
    Cancer. 1994 Jul 15;74(2):592-8 PMID: 8033038
  28. Cellular origin of the dermal-epidermal basement membrane.
    Dev Dyn. 1993 Aug;197(4):255-67 PMID: 8292823
  29. Hemidesmosomes: extracellular matrix/intermediate filament connectors.
    Exp Cell Res. 1994 Jul;213(1):1-11 PMID: 8020577
  30. Type VII collagen is a major structural component of anchoring fibrils.
    J Cell Biol. 1986 Oct;103(4):1577-86 PMID: 3771648
  31. Dual and asynchronous deposition of laminin chains at the epithelial-mesenchymal interface in the gut.
    Gastroenterology. 1992 Jun;102(6):1835-45 PMID: 1587403
  32. Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site.
    J Cell Biol. 1986 Dec;103(6 Pt 1):2457-65 PMID: 2430984
  33. The basement membrane and its involvement in carcinoma cell invasion.
    Acta Anat (Basel). 1995;152(2):69-84 PMID: 7660759
  34. Loss of co-localization of alpha 6 beta 4 integrin and collagen VII in bladder cancer.
    Am J Pathol. 1994 Apr;144(4):787-95 PMID: 7512792
  35. Laminin distribution patterns are closely related to liver metastasis in gastric cancer.
    Cancer. 1993 Feb 15;71(4):1201-6 PMID: 8435793
  36. Cloning of the LamA3 gene encoding the alpha 3 chain of the adhesive ligand epiligrin. Expression in wound repair.
    J Biol Chem. 1994 Sep 9;269(36):22779-87 PMID: 8077230
  37. The anchoring filament protein kalinin is synthesized and secreted as a high molecular weight precursor.
    J Biol Chem. 1992 Sep 5;267(25):17900-6 PMID: 1517226
  38. Differential expression of laminin isoforms and alpha 6-beta 4 integrin subunits in the developing human and mouse intestine.
    Dev Dyn. 1994 Sep;201(1):71-85 PMID: 7803849
  39. The laminins.
    Matrix Biol. 1994 Aug;14(4):275-81 PMID: 7827749
  40. Laminin is produced by early rat astrocytes in primary culture.
    J Cell Biol. 1983 Mar;96(3):920-4 PMID: 6339524
  41. Integrins and basement membrane proteins in skin carcinomas.
    Pathol Res Pract. 1994 Oct;190(9-10):950-4 PMID: 7899145
  42. Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis.
    Curr Opin Oncol. 1994 Jan;6(1):106-13 PMID: 7515692
  43. The borderline: basement membranes and the transition from premalignant to malignant neoplasia.
    Microsc Res Tech. 1994 Jun 15;28(3):216-25 PMID: 8068984
  44. Differential expression of laminin chains and their integrin receptors in human gastric mucosa.
    Am J Pathol. 1995 Oct;147(4):1123-32 PMID: 7573357
  45. Invading squamous cell carcinoma can retain a basal lamina. An immunohistochemical study using a monoclonal antibody to type IV collagen.
    Lab Invest. 1984 Jul;51(1):82-7 PMID: 6737996
  46. Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential?
    Acta Derm Venereol. 1994 Mar;74(2):101-5 PMID: 7911612
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1996-09-00
Pages
781-93
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1865153
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2