Abstract
The cadherin family of adhesion molecules are prime mediators of cell-cell interactions while the integrins predominantly mediate cell-matrix and to a lesser extent cell-cell binding specificity. We have recently shown that a human colon carcinoma cell line (SW1222) organizes into glandular structures, with well defined polarity when cultured in three-dimensional type I collagen gel. The current study indicates that SW1222 cells display high levels of E-cadherin (E-cd, epithelial cadherin) by western blotting and immunohistochemical staining. A monoclonal antibody (HECD-1) specific for human E-cd blocks cell-cell adhesion (100%) and inhibits (up to 75%) the glandular differentiation of SW1222 cells growing in collagen gel. Furthermore the anti-beta 1 integrin monoclonal antibody (mAb13) inhibits the glandular differentiation of SW1222 cells (61%) and their cellular binding to type I collagen (60%). However, no significant inhibition of cell-cell adhesion was demonstrated using mAb13 nor the anti-carcinoembryonic antigen monoclonal antibody (PR3B10). These results are consistent with E-cd being a cell-cell adhesion molecule expressed by SW1222 cells. These data indicate that E-cd and beta 1 integrins mediate cell-cell and cell-collagen interactions required for the induction and maintenance of the glandular differentiation of colorectal tumour cells. Thus the down-regulation or loss of E-cd and beta 1 integrins seen in poorly differentiated colorectal tumours may represent one of the abnormalities underlying their progression towards an undifferentiated phenotype in vivo.
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- Akiyama S. K., Yamada S. S., Chen W. T., Yamada K. M. Analysis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration, matrix assembly, and cytoskeletal organization. J Cell Biol. 1989 Aug;109(2):863–875. doi: 10.1083/jcb.109.2.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
- Benchimol S., Fuks A., Jothy S., Beauchemin N., Shirota K., Stanners C. P. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989 Apr 21;57(2):327–334. doi: 10.1016/0092-8674(89)90970-7. [DOI] [PubMed] [Google Scholar]
- Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol. 1990 Apr;110(4):1387–1404. doi: 10.1083/jcb.110.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Buono R., Pignatelli M., Bodmer W. F., Wright N. A. The role of the arginine-glycine-aspartic acid-directed cellular binding to type I collagen and rat mesenchymal cells in colorectal tumour differentiation. Differentiation. 1991 Mar;46(2):97–103. doi: 10.1111/j.1432-0436.1991.tb00870.x. [DOI] [PubMed] [Google Scholar]
- Duband J. L., Dufour S., Hatta K., Takeichi M., Edelman G. M., Thiery J. P. Adhesion molecules during somitogenesis in the avian embryo. J Cell Biol. 1987 May;104(5):1361–1374. doi: 10.1083/jcb.104.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edelman G. M., Crossin K. L. Cell adhesion molecules: implications for a molecular histology. Annu Rev Biochem. 1991;60:155–190. doi: 10.1146/annurev.bi.60.070191.001103. [DOI] [PubMed] [Google Scholar]
- Eidelman S., Damsky C. H., Wheelock M. J., Damjanov I. Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors. Am J Pathol. 1989 Jul;135(1):101–110. [PMC free article] [PubMed] [Google Scholar]
- Fidler I. J., Hart I. R. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982 Sep 10;217(4564):998–1003. doi: 10.1126/science.7112116. [DOI] [PubMed] [Google Scholar]
- Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giancotti F. G., Ruoslahti E. Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell. 1990 Mar 9;60(5):849–859. doi: 10.1016/0092-8674(90)90098-y. [DOI] [PubMed] [Google Scholar]
- Halvorsen T. B., Seim E. Degree of differentiation in colorectal adenocarcinomas: a multivariate analysis of the influence on survival. J Clin Pathol. 1988 May;41(5):532–537. doi: 10.1136/jcp.41.5.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
- Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
- Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
- Hynes R. O., Lander A. D. Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons. Cell. 1992 Jan 24;68(2):303–322. doi: 10.1016/0092-8674(92)90472-o. [DOI] [PubMed] [Google Scholar]
- Jass J. R., Atkin W. S., Cuzick J., Bussey H. J., Morson B. C., Northover J. M., Todd I. P. The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases. Histopathology. 1986 May;10(5):437–459. doi: 10.1111/j.1365-2559.1986.tb02497.x. [DOI] [PubMed] [Google Scholar]
- Larjava H., Peltonen J., Akiyama S. K., Yamada S. S., Gralnick H. R., Uitto J., Yamada K. M. Novel function for beta 1 integrins in keratinocyte cell-cell interactions. J Cell Biol. 1990 Mar;110(3):803–815. doi: 10.1083/jcb.110.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leibovitz A., Stinson J. C., McCombs W. B., 3rd, McCoy C. E., Mazur K. C., Mabry N. D. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976 Dec;36(12):4562–4569. [PubMed] [Google Scholar]
- Pignatelli M., Bodmer W. F. Genetics and biochemistry of collagen binding-triggered glandular differentiation in a human colon carcinoma cell line. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5561–5565. doi: 10.1073/pnas.85.15.5561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pignatelli M., Bodmer W. F. Integrin cell adhesion molecules and colorectal cancer. J Pathol. 1990 Oct;162(2):95–97. doi: 10.1002/path.1711620202. [DOI] [PubMed] [Google Scholar]
- Pignatelli M., Bodmer W. F. Integrin-receptor-mediated differentiation and growth inhibition are enhanced by transforming growth factor-beta in colorectal tumour cells grown in collagen gel. Int J Cancer. 1989 Sep 15;44(3):518–523. doi: 10.1002/ijc.2910440324. [DOI] [PubMed] [Google Scholar]
- Pignatelli M., Durbin H., Bodmer W. F. Carcinoembryonic antigen functions as an accessory adhesion molecule mediating colon epithelial cell-collagen interactions. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1541–1545. doi: 10.1073/pnas.87.4.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pignatelli M., Hanby A. M., Stamp G. W. Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumours. J Pathol. 1991 Sep;165(1):25–32. doi: 10.1002/path.1711650106. [DOI] [PubMed] [Google Scholar]
- Pignatelli M., Smith M. E., Bodmer W. F. Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br J Cancer. 1990 Apr;61(4):636–638. doi: 10.1038/bjc.1990.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rodriguez-Boulan E., Nelson W. J. Morphogenesis of the polarized epithelial cell phenotype. Science. 1989 Aug 18;245(4919):718–725. doi: 10.1126/science.2672330. [DOI] [PubMed] [Google Scholar]
- Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
- Shiozaki H., Tahara H., Oka H., Miyata M., Kobayashi K., Tamura S., Iihara K., Doki Y., Hirano S., Takeichi M. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed] [Google Scholar]
- Stamp G. W., Pignatelli M. Distribution of beta 1, alpha 1, alpha 2 and alpha 3 integrin chains in basal cell carcinomas. J Pathol. 1991 Apr;163(4):307–313. doi: 10.1002/path.1711630407. [DOI] [PubMed] [Google Scholar]
- Sztul E. S., Biemesderfer D., Caplan M. J., Kashgarian M., Boyer J. L. Localization of Na+,K+-ATPase alpha-subunit to the sinusoidal and lateral but not canalicular membranes of rat hepatocytes. J Cell Biol. 1987 May;104(5):1239–1248. doi: 10.1083/jcb.104.5.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
- Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988 Apr;102(4):639–655. doi: 10.1242/dev.102.4.639. [DOI] [PubMed] [Google Scholar]
- Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]



