Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Apr 2;113(2):437–449. doi: 10.1083/jcb.113.2.437

92-kD type IV collagenase mediates invasion of human cytotrophoblasts

PMCID: PMC2288933  PMID: 1849141

Abstract

The specialized interaction between embryonic and maternal tissues is unique to mammalian development. This interaction begins with invasion of the uterus by the first differentiated embryonic cells, the trophoblasts, and culminates in formation of the placenta. The transient tumor-like behavior of cytotrophoblasts, which peaks early in pregnancy, is developmentally regulated. Likewise, in culture only early-gestation human cytotrophoblasts invade a basement membrane-like substrate. These invasive cells synthesize both metalloproteinases and urokinase-type plasminogen activator. Metalloproteinase inhibitors and a function-perturbing antibody specific for the 92-kD type IV collagen- degrading metalloproteinase completely inhibited cytotrophoblast invasion, whereas inhibitors of the plasminogen activator system had only a partial (20-40%) inhibitory effect. We conclude that the 92-kD type IV collagenase is critical for cytotrophoblast invasion.

Full Text

The Full Text of this article is available as a PDF (3.9 MB).

Selected References

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

  1. Albini A., Iwamoto Y., Kleinman H. K., Martin G. R., Aaronson S. A., Kozlowski J. M., McEwan R. N. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987 Jun 15;47(12):3239–3245. [PubMed] [Google Scholar]
  2. Alexander C. M., Werb Z. Proteinases and extracellular matrix remodeling. Curr Opin Cell Biol. 1989 Oct;1(5):974–982. doi: 10.1016/0955-0674(89)90068-9. [DOI] [PubMed] [Google Scholar]
  3. Arceci R. J., Shanahan F., Stanley E. R., Pollard J. W. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8818–8822. doi: 10.1073/pnas.86.22.8818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Auersperg N., Kruk P. A., MacLaren I. A., Watt F. M., Mydral S. E. Heterogeneous expression of keratin, involucrin, and extracellular matrix among subpopulations of a poorly differentiated human cervical carcinoma: possible relationships to patterns of invasion. Cancer Res. 1989 Jun 1;49(11):3007–3014. [PubMed] [Google Scholar]
  5. Babalola G. O., Coutifaris C., Soto E. A., Kliman H. J., Shuman H., Strauss J. F., 3rd Aggregation of dispersed human cytotrophoblastic cells: lessons relevant to the morphogenesis of the placenta. Dev Biol. 1990 Jan;137(1):100–108. doi: 10.1016/0012-1606(90)90011-7. [DOI] [PubMed] [Google Scholar]
  6. Bergman B. L., Scott R. W., Bajpai A., Watts S., Baker J. B. Inhibition of tumor-cell-mediated extracellular matrix destruction by a fibroblast proteinase inhibitor, protease nexin I. Proc Natl Acad Sci U S A. 1986 Feb;83(4):996–1000. doi: 10.1073/pnas.83.4.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bernhard E. J., Muschel R. J., Hughes E. N. Mr 92,000 gelatinase release correlates with the metastatic phenotype in transformed rat embryo cells. Cancer Res. 1990 Jul 1;50(13):3872–3877. [PubMed] [Google Scholar]
  8. Birkedal-Hansen H., Birkedal-Hansen B., Windsor L. J., Lin H. Y., Taylor R. E., Moore W. G. Use of inhibitory (anti-catalytic) antibodies to study extracellular proteolysis. Immunol Invest. 1989 Jan-May;18(1-4):211–224. doi: 10.3109/08820138909112238. [DOI] [PubMed] [Google Scholar]
  9. Brenner C. A., Adler R. R., Rappolee D. A., Pedersen R. A., Werb Z. Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development. Genes Dev. 1989 Jun;3(6):848–859. doi: 10.1101/gad.3.6.848. [DOI] [PubMed] [Google Scholar]
  10. Cajot J. F., Schleuning W. D., Medcalf R. L., Bamat J., Testuz J., Liebermann L., Sordat B. Mouse L cells expressing human prourokinase-type plasminogen activator: effects on extracellular matrix degradation and invasion. J Cell Biol. 1989 Aug;109(2):915–925. doi: 10.1083/jcb.109.2.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Charbonneau H., Tonks N. K., Kumar S., Diltz C. D., Harrylock M., Cool D. E., Krebs E. G., Fischer E. H., Walsh K. A. Human placenta protein-tyrosine-phosphatase: amino acid sequence and relationship to a family of receptor-like proteins. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5252–5256. doi: 10.1073/pnas.86.14.5252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chen W. T. Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells. J Exp Zool. 1989 Aug;251(2):167–185. doi: 10.1002/jez.1402510206. [DOI] [PubMed] [Google Scholar]
  13. Chin J. R., Murphy G., Werb Z. Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates. J Biol Chem. 1985 Oct 5;260(22):12367–12376. [PubMed] [Google Scholar]
  14. Collier I. E., Wilhelm S. M., Eisen A. Z., Marmer B. L., Grant G. A., Seltzer J. L., Kronberger A., He C. S., Bauer E. A., Goldberg G. I. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988 May 15;263(14):6579–6587. [PubMed] [Google Scholar]
  15. Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
  16. Denker H. W. Implantation. The role of proteinases, and blockage of implantation by proteinase inhibitors. Adv Anat Embryol Cell Biol. 1977;53(5):3–123. [PubMed] [Google Scholar]
  17. Enders A. C. Cytology of human early implantation. Res Reprod. 1976 Sep;8(5):1–2. [PubMed] [Google Scholar]
  18. Fairbairn S., Gilbert R., Ojakian G., Schwimmer R., Quigley J. P. The extracellular matrix of normal chick embryo fibroblasts: its effect on transformed chick fibroblasts and its proteolytic degradation by the transformants. J Cell Biol. 1985 Nov;101(5 Pt 1):1790–1798. doi: 10.1083/jcb.101.5.1790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Feinberg R. F., Kao L. C., Haimowitz J. E., Queenan J. T., Jr, Wun T. C., Strauss J. F., 3rd, Kliman H. J. Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts. Lab Invest. 1989 Jul;61(1):20–26. [PubMed] [Google Scholar]
  20. Fisher S. J., Cui T. Y., Zhang L., Hartman L., Grahl K., Zhang G. Y., Tarpey J., Damsky C. H. Adhesive and degradative properties of human placental cytotrophoblast cells in vitro. J Cell Biol. 1989 Aug;109(2):891–902. doi: 10.1083/jcb.109.2.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Glass R. H., Aggeler J., Spindle A., Pedersen R. A., Werb Z. Degradation of extracellular matrix by mouse trophoblast outgrowths: a model for implantation. J Cell Biol. 1983 Apr;96(4):1108–1116. doi: 10.1083/jcb.96.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. HE C. S., Wilhelm S. M., Pentland A. P., Marmer B. L., Grant G. A., Eisen A. Z., Goldberg G. I. Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2632–2636. doi: 10.1073/pnas.86.8.2632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Han V. K., Hunter E. S., 3rd, Pratt R. M., Zendegui J. G., Lee D. C. Expression of rat transforming growth factor alpha mRNA during development occurs predominantly in the maternal decidua. Mol Cell Biol. 1987 Jul;7(7):2335–2343. doi: 10.1128/mcb.7.7.2335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
  25. Hendrix M. J., Seftor E. A., Seftor R. E., Fidler I. J. A simple quantitative assay for studying the invasive potential of high and low human metastatic variants. Cancer Lett. 1987 Dec;38(1-2):137–147. doi: 10.1016/0304-3835(87)90209-6. [DOI] [PubMed] [Google Scholar]
  26. Herron G. S., Banda M. J., Clark E. J., Gavrilovic J., Werb Z. Secretion of metalloproteinases by stimulated capillary endothelial cells. II. Expression of collagenase and stromelysin activities is regulated by endogenous inhibitors. J Biol Chem. 1986 Feb 25;261(6):2814–2818. [PubMed] [Google Scholar]
  27. Heussen C., Dowdle E. B. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem. 1980 Feb;102(1):196–202. doi: 10.1016/0003-2697(80)90338-3. [DOI] [PubMed] [Google Scholar]
  28. Ignotz R. A., Heino J., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Regulation of vitronectin receptor and LFA-1. J Biol Chem. 1989 Jan 5;264(1):389–392. [PubMed] [Google Scholar]
  29. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  30. Kliman H. J., Feinberg R. F. Human trophoblast-extracellular matrix (ECM) interactions in vitro: ECM thickness modulates morphology and proteolytic activity. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3057–3061. doi: 10.1073/pnas.87.8.3057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kliman H. J., Nestler J. E., Sermasi E., Sanger J. M., Strauss J. F., 3rd Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology. 1986 Apr;118(4):1567–1582. doi: 10.1210/endo-118-4-1567. [DOI] [PubMed] [Google Scholar]
  32. Kramer R. H., Bensch K. G., Wong J. Invasion of reconstituted basement membrane matrix by metastatic human tumor cells. Cancer Res. 1986 Apr;46(4 Pt 2):1980–1989. [PubMed] [Google Scholar]
  33. Kurman R. J., Main C. S., Chen H. C. Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features. Placenta. 1984 Jul-Aug;5(4):349–369. doi: 10.1016/s0143-4004(84)80015-6. [DOI] [PubMed] [Google Scholar]
  34. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  35. Laiho M., Saksela O., Keski-Oja J. Transforming growth factor-beta induction of type-1 plasminogen activator inhibitor. Pericellular deposition and sensitivity to exogenous urokinase. J Biol Chem. 1987 Dec 25;262(36):17467–17474. [PubMed] [Google Scholar]
  36. Lichtner R. B., Moskwa P. S., Nicolson G. L. Heterogeneous expression of cytokeratins in metastatic mammary adenocarcinoma cells in vitro and in vivo. Invasion Metastasis. 1987;7(6):367–383. [PubMed] [Google Scholar]
  37. Liotta L. A., Abe S., Robey P. G., Martin G. R. Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc Natl Acad Sci U S A. 1979 May;76(5):2268–2272. doi: 10.1073/pnas.76.5.2268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Liotta L. A., Rao C. N., Wewer U. M. Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem. 1986;55:1037–1057. doi: 10.1146/annurev.bi.55.070186.005133. [DOI] [PubMed] [Google Scholar]
  39. Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990 Apr;6(4):121–125. doi: 10.1016/0168-9525(90)90126-q. [DOI] [PubMed] [Google Scholar]
  40. McKerrow J. H., Pino-Heiss S., Lindquist R., Werb Z. Purification and characterization of an elastinolytic proteinase secreted by cercariae of Schistosoma mansoni. J Biol Chem. 1985 Mar 25;260(6):3703–3707. [PubMed] [Google Scholar]
  41. Mignatti P., Robbins E., Rifkin D. B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell. 1986 Nov 21;47(4):487–498. doi: 10.1016/0092-8674(86)90613-6. [DOI] [PubMed] [Google Scholar]
  42. Miller E. J., Harris E. D., Jr, Chung E., Finch J. E., Jr, McCroskery P. A., Butler W. T. Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Biochemistry. 1976 Feb 24;15(4):787–792. doi: 10.1021/bi00649a009. [DOI] [PubMed] [Google Scholar]
  43. Murphy G., McAlpine C. G., Poll C. T., Reynolds J. J. Purification and characterization of a bone metalloproteinase that degrades gelatin and types IV and V collagen. Biochim Biophys Acta. 1985 Sep 20;831(1):49–58. doi: 10.1016/0167-4838(85)90148-7. [DOI] [PubMed] [Google Scholar]
  44. Murphy G., Ward R., Hembry R. M., Reynolds J. J., Kühn K., Tryggvason K. Characterization of gelatinase from pig polymorphonuclear leucocytes. A metalloproteinase resembling tumour type IV collagenase. Biochem J. 1989 Mar 1;258(2):463–472. doi: 10.1042/bj2580463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Nomura S., Hogan B. L., Wills A. J., Heath J. K., Edwards D. R. Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA. Development. 1989 Mar;105(3):575–583. doi: 10.1242/dev.105.3.575. [DOI] [PubMed] [Google Scholar]
  46. Okada Y., Nagase H., Harris E. D., Jr A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. Purification and characterization. J Biol Chem. 1986 Oct 25;261(30):14245–14255. [PubMed] [Google Scholar]
  47. Ossowski L. In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. J Cell Biol. 1988 Dec;107(6 Pt 1):2437–2445. doi: 10.1083/jcb.107.6.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Plow E. F., Freaney D. E., Plescia J., Miles L. A. The plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type. J Cell Biol. 1986 Dec;103(6 Pt 1):2411–2420. doi: 10.1083/jcb.103.6.2411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Queenan J. T., Jr, Kao L. C., Arboleda C. E., Ulloa-Aguirre A., Golos T. G., Cines D. B., Strauss J. F., 3rd Regulation of urokinase-type plasminogen activator production by cultured human cytotrophoblasts. J Biol Chem. 1987 Aug 15;262(23):10903–10906. [PubMed] [Google Scholar]
  50. Quigley J. P., Gold L. I., Schwimmer R., Sullivan L. M. Limited cleavage of cellular fibronectin by plasminogen activator purified from transformed cells. Proc Natl Acad Sci U S A. 1987 May;84(9):2776–2780. doi: 10.1073/pnas.84.9.2776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Quigley J. P. Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator. Cell. 1979 May;17(1):131–141. doi: 10.1016/0092-8674(79)90301-5. [DOI] [PubMed] [Google Scholar]
  52. Regenstreif L. J., Rossant J. Expression of the c-fms proto-oncogene and of the cytokine, CSF-1, during mouse embryogenesis. Dev Biol. 1989 May;133(1):284–294. doi: 10.1016/0012-1606(89)90319-9. [DOI] [PubMed] [Google Scholar]
  53. Reich R., Thompson E. W., Iwamoto Y., Martin G. R., Deason J. R., Fuller G. C., Miskin R. Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells. Cancer Res. 1988 Jun 15;48(12):3307–3312. [PubMed] [Google Scholar]
  54. Repesh L. A. A new in vitro assay for quantitating tumor cell invasion. Invasion Metastasis. 1989;9(3):192–208. [PubMed] [Google Scholar]
  55. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Saksela O., Rifkin D. B. Cell-associated plasminogen activation: regulation and physiological functions. Annu Rev Cell Biol. 1988;4:93–126. doi: 10.1146/annurev.cb.04.110188.000521. [DOI] [PubMed] [Google Scholar]
  57. Sappino A. P., Huarte J., Belin D., Vassalli J. D. Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos. J Cell Biol. 1989 Nov;109(5):2471–2479. doi: 10.1083/jcb.109.5.2471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schmid T. M., Mayne R., Jeffrey J. J., Linsenmayer T. F. Type X collagen contains two cleavage sites for a vertebrate collagenase. J Biol Chem. 1986 Mar 25;261(9):4184–4189. [PubMed] [Google Scholar]
  59. Schultz R. M., Silberman S., Persky B., Bajkowski A. S., Carmichael D. F. Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells. Cancer Res. 1988 Oct 1;48(19):5539–5545. [PubMed] [Google Scholar]
  60. Seltzer J. L., Eisen A. Z., Bauer E. A., Morris N. P., Glanville R. W., Burgeson R. E. Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (gelatinase) derived from human skin. J Biol Chem. 1989 Mar 5;264(7):3822–3826. [PubMed] [Google Scholar]
  61. Simson J. A., Dom R., Chao J., Woodley C., Chao L., Margolius H. S. Immunocytochemical localization of tissue kallikrein in brain ventricular epithelium and hypothalamic cell bodies. J Histochem Cytochem. 1985 Sep;33(9):951–953. doi: 10.1177/33.9.3894505. [DOI] [PubMed] [Google Scholar]
  62. Stephens R. W., Pöllänen J., Tapiovaara H., Leung K. C., Sim P. S., Salonen E. M., Rønne E., Behrendt N., Danø K., Vaheri A. Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol. 1989 May;108(5):1987–1995. doi: 10.1083/jcb.108.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Strickland S., Reich E., Sherman M. I. Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell. 1976 Oct;9(2):231–240. doi: 10.1016/0092-8674(76)90114-8. [DOI] [PubMed] [Google Scholar]
  64. Sutherland A. E., Speed T. P., Calarco P. G. Inner cell allocation in the mouse morula: the role of oriented division during fourth cleavage. Dev Biol. 1990 Jan;137(1):13–25. doi: 10.1016/0012-1606(90)90003-2. [DOI] [PubMed] [Google Scholar]
  65. Thorgeirsson U. P., Liotta L. A., Kalebic T., Margulies I. M., Thomas K., Rios-Candelore M., Russo R. G. Effect of natural protease inhibitors and a chemoattractant on tumor cell invasion in vitro. J Natl Cancer Inst. 1982 Nov;69(5):1049–1054. [PubMed] [Google Scholar]
  66. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Tullberg K. F., Burger M. M. Selection of B16 melanoma cells with increased metastatic potential and low intercellular cohesion using Nuclepore filters. Invasion Metastasis. 1985;5(1):1–15. [PubMed] [Google Scholar]
  68. Weingarten H., Martin R., Feder J. Synthetic substrates of vertebrate collagenase. Biochemistry. 1985 Nov 5;24(23):6730–6734. doi: 10.1021/bi00344a064. [DOI] [PubMed] [Google Scholar]
  69. Welgus H. G., Fliszar C. J., Seltzer J. L., Schmid T. M., Jeffrey J. J. Differential susceptibility of type X collagen to cleavage by two mammalian interstitial collagenases and 72-kDa type IV collagenase. J Biol Chem. 1990 Aug 15;265(23):13521–13527. [PubMed] [Google Scholar]
  70. Werb Z. Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions. J Exp Med. 1978 Jun 1;147(6):1695–1712. doi: 10.1084/jem.147.6.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Werb Z., Mainardi C. L., Vater C. A., Harris E. D., Jr Endogenous activiation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. N Engl J Med. 1977 May 5;296(18):1017–1023. doi: 10.1056/NEJM197705052961801. [DOI] [PubMed] [Google Scholar]
  72. Wilhelm S. M., Collier I. E., Marmer B. L., Eisen A. Z., Grant G. A., Goldberg G. I. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989 Oct 15;264(29):17213–17221. [PubMed] [Google Scholar]

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

RESOURCES