Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1988 Mar 1; 106(3): 925–930.
PMCID: PMC2115099

Inhibition of in vitro tumor cell invasion by Arg-Gly-Asp-containing synthetic peptides [published erratum appears in J Cell Biol 1989 Jun;108(6):following 2546]


The interaction of cells with extracellular matrix components such as fibronectin, vitronectin, and type I collagen has been shown to be mediated through a family of cell-surface receptors that specifically recognize an arginine-glycine-aspartic acid (RGD) amino acid sequence within each protein. Synthetic peptides containing the RGD sequence can inhibit these receptor-ligand interactions. Here, we use novel RGD- containing synthetic peptides with different inhibition properties to investigate the role of the various RGD receptors in tumor cell invasion. The RGD-containing peptides used include peptides that inhibit the attachment of cells to fibronectin and vitronectin, a peptide that inhibits attachment to fibronectin but not to vitronectin, a cyclic peptide with the opposite specificity, and a peptide, GRGDTP, that inhibits attachment to type I collagen in addition to inhibiting attachment to fibronectin and vitronectin. The penetration of two human melanoma cell lines and a glioblastoma cell line through the human amniotic basement membrane and its underlying stroma was inhibited by all of the RGD-containing peptides except for the one that inhibits only the vitronectin attachment. Various control peptides lacking RGD showed essentially no inhibition. This inhibitory effect on cell invasion was dose-dependent and nontoxic. A hexapeptide, GRGDTP, that inhibits the attachment of cells to type I collagen in addition to inhibiting fibronectin- and vitronectin-mediated attachment was more inhibitory than those RGD peptides that inhibit only fibronectin and vitronectin attachment. Analysis of the location of these cells that were prevented from invading indicated that they attached to the amniotic basement membrane but did not proceed further into the tissue. These results suggest that interactions between RGD-containing extracellular matrix adhesion proteins and cells are necessary for cell invasion through tissues and that fibronectin and type I collagen are important for this process.

Full Text

The Full Text of this article is available as a PDF (837K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aumailley M, Timpl R. Attachment of cells to basement membrane collagen type IV. J Cell Biol. 1986 Oct;103(4):1569–1575. [PMC free article] [PubMed]
  • Bronner-Fraser M. An antibody to a receptor for fibronectin and laminin perturbs cranial neural crest development in vivo. Dev Biol. 1986 Oct;117(2):528–536. [PubMed]
  • Chen JM, Chen WT. Fibronectin-degrading proteases from the membranes of transformed cells. Cell. 1987 Jan 30;48(2):193–203. [PubMed]
  • Dedhar S, Ruoslahti E, Pierschbacher MD. A cell surface receptor complex for collagen type I recognizes the Arg-Gly-Asp sequence. J Cell Biol. 1987 Mar;104(3):585–593. [PMC free article] [PubMed]
  • Duband JL, Thiery JP. Distribution of fibronectin in the early phase of avian cephalic neural crest cell migration. Dev Biol. 1982 Oct;93(2):308–323. [PubMed]
  • Erickson CA, Tosney KW, Weston JA. Analysis of migratory behavior of neural crest and fibroblastic cells in embryonic tissues. Dev Biol. 1980 Jun 1;77(1):142–156. [PubMed]
  • Fidler IJ, Gersten DM, Hart IR. The biology of cancer invasion and metastasis. Adv Cancer Res. 1978;28:149–250. [PubMed]
  • Gehlsen KR, Wagner HN, Jr, Hendrix MJ. Membrane invasion culture system (MICS). Med Instrum. 1984 Sep-Oct;18(5):268–271. [PubMed]
  • Gehlsen KR, Hendrix MJ. In vitro assay demonstrates similar invasion profiles for B16F1 and B16F10 murine melanoma cells. Cancer Lett. 1986 Feb;30(2):207–212. [PubMed]
  • Goodman SL, Newgreen D. Do cells show an inverse locomotory response to fibronectin and laminin substrates? EMBO J. 1985 Nov;4(11):2769–2771. [PMC free article] [PubMed]
  • Goodman SL, Deutzmann R, von der Mark K. Two distinct cell-binding domains in laminin can independently promote nonneuronal cell adhesion and spreading. J Cell Biol. 1987 Jul;105(1):589–598. [PMC free article] [PubMed]
  • Graf J, Iwamoto Y, Sasaki M, Martin GR, Kleinman HK, Robey FA, Yamada Y. Identification of an amino acid sequence in laminin mediating cell attachment, chemotaxis, and receptor binding. Cell. 1987 Mar 27;48(6):989–996. [PubMed]
  • Hayman EG, Pierschbacher MD, Ruoslahti E. Detachment of cells from culture substrate by soluble fibronectin peptides. J Cell Biol. 1985 Jun;100(6):1948–1954. [PMC free article] [PubMed]
  • Hayman EG, Pierschbacher MD, Suzuki S, Ruoslahti E. Vitronectin--a major cell attachment-promoting protein in fetal bovine serum. Exp Cell Res. 1985 Oct;160(2):245–258. [PubMed]
  • Hendrix MJ, Gehlsen KR, Wagner HN, Jr, Rodney SR, Misiorowski RL, Meyskens FL., Jr In vitro quantification of melanoma tumor cell invasion. Clin Exp Metastasis. 1985 Oct-Dec;3(4):221–233. [PubMed]
  • Honig MG, Hume RI. Fluorescent carbocyanine dyes allow living neurons of identified origin to be studied in long-term cultures. J Cell Biol. 1986 Jul;103(1):171–187. [PMC free article] [PubMed]
  • Horwitz A, Duggan K, Greggs R, Decker C, Buck C. The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin. J Cell Biol. 1985 Dec;101(6):2134–2144. [PMC free article] [PubMed]
  • Humphries MJ, Olden K, Yamada KM. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science. 1986 Jul 25;233(4762):467–470. [PubMed]
  • Humphries MJ, Akiyama SK, Komoriya A, Olden K, Yamada KM. Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion. J Cell Biol. 1986 Dec;103(6 Pt 2):2637–2647. [PMC free article] [PubMed]
  • Hynes RO, Yamada KM. Fibronectins: multifunctional modular glycoproteins. J Cell Biol. 1982 Nov;95(2 Pt 1):369–377. [PMC free article] [PubMed]
  • Kozlowski JM, Hart IR, Fidler IJ, Hanna N. A human melanoma line heterogeneous with respect to metastatic capacity in athymic nude mice. J Natl Cancer Inst. 1984 Apr;72(4):913–917. [PubMed]
  • Lacovara J, Cramer EB, Quigley JP. Fibronectin enhancement of directed migration of B16 melanoma cells. Cancer Res. 1984 Apr;44(4):1657–1663. [PubMed]
  • Liotta LA, Lee CW, Morakis DJ. New method for preparing large surfaces of intact human basement membrane for tumor invasion studies. Cancer Lett. 1980 Dec;11(2):141–152. [PubMed]
  • Liotta LA, Rao CN, Barsky SH. Tumor invasion and the extracellular matrix. Lab Invest. 1983 Dec;49(6):636–649. [PubMed]
  • Liotta LA, Rao CN, Wewer UM. Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem. 1986;55:1037–1057. [PubMed]
  • McCarthy JB, Furcht LT. Laminin and fibronectin promote the haptotactic migration of B16 mouse melanoma cells in vitro. J Cell Biol. 1984 Apr;98(4):1474–1480. [PMC free article] [PubMed]
  • McCarthy JB, Hagen ST, Furcht LT. Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells. J Cell Biol. 1986 Jan;102(1):179–188. [PMC free article] [PubMed]
  • Mignatti P, Robbins E, Rifkin DB. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell. 1986 Nov 21;47(4):487–498. [PubMed]
  • Nicolson GL. Cell surface molecules and tumor metastasis. Regulation of metastatic phenotypic diversity. Exp Cell Res. 1984 Jan;150(1):3–22. [PubMed]
  • Pierschbacher MD, Ruoslahti E. Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5985–5988. [PMC free article] [PubMed]
  • Pierschbacher MD, Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature. 1984 May 3;309(5963):30–33. [PubMed]
  • Pierschbacher MD, Ruoslahti E. Influence of stereochemistry of the sequence Arg-Gly-Asp-Xaa on binding specificity in cell adhesion. J Biol Chem. 1987 Dec 25;262(36):17294–17298. [PubMed]
  • Pöllänen J, Saksela O, Salonen EM, Andreasen P, Nielsen L, Danø K, Vaheri A. Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells. J Cell Biol. 1987 Apr;104(4):1085–1096. [PMC free article] [PubMed]
  • Pytela R, Pierschbacher MD, Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985 Jan;40(1):191–198. [PubMed]
  • Pytela R, Pierschbacher MD, Ruoslahti E. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5766–5770. [PMC free article] [PubMed]
  • Ruoslahti E. Fibronectin in cell adhesion and invasion. Cancer Metastasis Rev. 1984;3(1):43–51. [PubMed]
  • Ruoslahti E, Hayman EG, Pierschbacher M, Engvall E. Fibronectin: purification, immunochemical properties, and biological activities. Methods Enzymol. 1982;82(Pt A):803–831. [PubMed]
  • Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. [PubMed]
  • Savagner P, Imhof BA, Yamada KM, Thiery JP. Homing of hemopoietic precursor cells to the embryonic thymus: characterization of an invasive mechanism induced by chemotactic peptides. J Cell Biol. 1986 Dec;103(6 Pt 2):2715–2727. [PMC free article] [PubMed]
  • Yamada KM, Kennedy DW. Amino acid sequence specificities of an adhesive recognition signal. J Cell Biochem. 1985;28(2):99–104. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...