[en] Wound repair involves many processes including cell migration, provisional matrix deposition, and remodeling. All of these processes are likely to be affected by matrix-modifying enzymes. Members of the matrix metalloproteinases family are physiologic mediators of the extracellular matrix degradation. Within this matrix metalloproteinases family, stromelysins can degrade many components of the extracellular matrix. We therefore tested the hypothesis that stromelysins could be produced by human surface respiratory epithelial (HSRE) cells repairing a wound. Experimental wounds were created in vitro in HSRE cell cultures and in situ in human bronchial mucosa maintained in organ culture. Stromelysin production was measured by casein-gel zymography in cellular protein extracts derived from repairing migratory and nonrepairing stationary cells of wounded HSRE cell cultures. Stromelysin-producing cells present in cell and tissue cultures were localized and characterized using immunofluorescence techniques. Zymographic and immunofluorescence techniques showed that stromelysins were produced exclusively by the migratory HSRE cells. Zymogram analysis showed that stromelysins were overexpressed and overactivated during the wound repair process, with the maximal production observed at wound closure. Using an anti-cytokeratin 14 antibody, we identified stromelysin-3-producing cells as basal epithelial cells. Moreover, most stromelysin-3-producing cells expressed the mesenchymal marker vimentin. Similar to stromelysins localization, vimentin-positive HSRE cells were exclusively located in the wounded area, and they were also positive to cytokeratin 14. In conclusion, stromelysins are suggested to be involved in HSRE cell migration and extracellular matrix remodeling during wound repair. Furthermore, stromelysin production by repairing HSRE cells is linked to the acquisition of a mesenchymal phenotype. HSRE cell migration may then be associated with the shift from an epithelial to a mesenchymal phenotype.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Buisson, A. C.
Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Polette, M.
Zahm, J. M.
Birembaut, P.
Tournier, J. M.
Language :
English
Title :
Wound repair-induced expression of a stromelysins is associated with the acquisition of a mesenchymal phenotype in human respiratory epithelial cells
Publication date :
1996
Journal title :
Laboratory Investigation
ISSN :
0023-6837
eISSN :
1530-0307
Publisher :
Lippincott Williams & Wilkins, Hagerstown, United States - Maryland
Allan JA, Hembry RM, Angal S, Reynolds JJ, and Murphy G (1991). Binding of latent and high Mr active forms of stromelysin to collagen is mediated by the C-terminal domain. J Cell Sci 99:789-795.
Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhjacer OL, Chenard MP, Rio MC, and Chambon P (1990). A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348:699-704.
Basset P, Wolf C, and Chambon P (1993). Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: A review. Breast Cancer Res Treat 24:185-193.
Ben-Ze'ev A (1985). Cell-cell interaction and cell configuration related control of cytokeratins and vimentin expression in epithelial cells and in fibroblasts. Ann N Y Acad Sci 455:597-613.
Boyer B, Tucker GC, Vallés AM, Franke WW, and Thiery JP (1989). Rearrangements of desmosomal and cytoskeletal proteins during the transition from epithelial to fibroblastoid organization in cultured rat bladder carcinoma cells. J Cell Biol 109:1495-1509.
Chevillard M, Hinnrasky J, Pierrot D, Zahm J-M, Klossek J-M, and Puchelle E (1993). Differentiation of human surface upper airway epithelial cells in primary culture on a floating collagen gel. Epithelial Cell Biol 2:17-25.
Clark RAF and Henson PM, editors (1988). The molecular and cellular biology of wound repair. New York: Plenum Press.
Connell ND and Rheinwald JG (1983). Regulation of the cytoskeleton in mesothelial cells: Reversible loss of keratin and increase in vimentin during rapid growth in culture. Cell 34:245-253.
Docherty AJP and Murphy G (1990). The tissue metalloproteinase family and the inhibitors TIMP: A study using cDNAs and recombinant proteins. Ann Rheum Dis 49:469-479.
Dulbecco R, Allen R, Okada S, and Bowman M (1983). Functional changes of intermediate filaments in fibroblastic cells revealed by a monoclonal antibody. Proc Natl Acad Sci USA 80:1915-1918.
Dvorak HF (1986). Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650-1659.
Freije JMP, Dìez-Itza I, Balbin M, Sànchez LM, Blasco R, Tolivia J, and Lòpez-Otìn C (1994). Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 269:16766-16773.
Gilles C, Polette M, Piette J, Birembaut P, and Foidart J-M (1994). Epithelial-to-mesenchymal transition in HPV-33-transfected cervical keratinocytes is associated with increased invasiveness and expression of gelatinase A. Int J Cancer 59:661-666.
Girard MT, Matsubara M, Kublin C, Tessier MJ, Cintron C, and Fini ME (1993). Stromal fibroblasts synthetize collagenase and stromelysin during long-term tissue remodeling. J Cell Sci 104:1001-1011.
Goldberg GI, Strongin A, Collier IE, Genrich LT, and Marmer BL (1992). Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem 267: 4583-4591.
Goldman RD, Goldman AE, Green KJ, Jones JCR, Jones SM, and Yang HY (1986). Intermediate filaments networks: Organization and possible functions of a diverse group of cytoskeletal elements. J Cell Sci Suppl 5:69.
Gröne H-J, Weber K, Gröne E, Helmchen U, and Osborn M (1987). Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney. Am J Pathol 129:1-8.
Jackson BW, Grund C, Schmid E, Burki K, Franke WW, and Illmensee K (1980). Formation of cytoskeletal elements during mouse embryogenesis. Differentiation 17:161-189.
Kleiner DE and Stetler-Stevenson WG (1994). Quantitative zymography: Detection of picogram quantities of gelatinases. Anal Biochem 218:325-329.
Lane EB, Goodman SL, and Trejdosiewicz LK (1982). Disruption of the keratin filament network during epithelial cell division. EMBO J 1:1365-1372.
Lane EB, Hogan BLM, Kurkinen M, and Garrels JI (1983). Co-expression of vimentin and cytokeratins in parietal endoderm cells of early mouse embryo. Nature 303:701-704.
Lefebvre O, Wolf C, Limacher J-M, Hutin P, Wendling C, LeMeur M, Basset P, and Rio M-C (1992). The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol 119:997-1002.
Man SFP and Hulbert WC (1988). Airway repair and adaptation to inhalation injury. In: Loke J, editor. Pathophysiology and treatment of inhalation injuries. New York: Marcel Dekker, 1-47.
Matrisian LM (1990). Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121-125.
McDonnell S and Matrisian LM (1990). Stomelysin in tumor progression and metastasis. Cancer Metast Rev 9:305-319.
Mignatti P, Welgus HG, and Rifkin DB (1988). Role of degradative enzymes in wound healing. In: Clark RAF and Henson PM, editors. The molecular and cellular biology of wound repair. New York: Plenum Press, 497-523.
Moll R, Franke WW, Schiller D, Geiger B, and Krepler R (1982). The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11-24.
Muller D, Quantin B, Gesnel MC, Millon-Collard R, Abecassis J, and Breathnach R (1988). The collagenase gene family in human consists of at least four members. Biochem J 253: 187-192.
Muller D, Wolf C, Abecassis J, Millon R, Engelmann A, Bronner G, Rouyer N, Rio M-C, Eber M, Methlin G, Chambon P, and Basset P (1993). Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res 53:165-169.
Murphy G, Segain JP, O'Shea M, Cockett M, Ioannou C, Lefebvre O, Chambon P, and Basset P (1993). The 28-kDa N-terminal domain of mouse stromelysin-3 has the general properties of a weak metalloproteinase. J Biol Chem 268: 15435-15441.
Nagase H, Ogata Y, Suzuki K, Enghild JJ, and Salvesen G (1991). Substrate specificities and activation mechanisms of matrix metalloproteinases. Biochem Soc Trans 19:715-718.
Nawrocki B, Polette M, Clavel C, Morrone A, Eschard JP, Etienne JC, and Birembaut P (1994). Expression of stromelysin 3 and tissue inhibitors of matrix metallo-proteinases, Timp-1 and Timp-2, in rheumatoid arthritis. Pathol Res Pract 190:690-696.
Noël A, Santavicca M, Stoll I, L'Hoir C, Staub A, Murphy G, Rio MC, and Basset P (1995). Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities. J Biol Chem 270:22866-22872.
Ogata Y, Enghild JJ, and Nagase H (1992). Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 267:3581-3584.
Okada Y, Takeuchi N, Tomita K, Nakanishi I, and Nagase H (1989). Immunolocalisation of matrix metalloproteinase 3 (stromelysin) in rheumatoid synovioblasts (B cells): Correlation with rheumatoid arthritis. Ann Rheum Dis 48:645-653.
Pei D, Majmudar G, and Weiss SJ (1994). Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3. J Biol Chem 269:25849-25855.
Polette M, Clavel C, Cockett M, Girod de Bentzmann S, Murphy G, and Birembaut P (1993a). Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. Invasion Metast 13:31-37.
Polette M, Clavel C, De Clerck YA, and Birembaut P (1993b). Localization by in situ hybridization of mRNAs encoding stromelysin 3 and tissue inhibitors of metallo-proteinases TIMP-1 and TIMP-2 in human head and neck carcinomas. Pathol Res Pract 189:1052-1057.
Polette M, Clavel C, Muller D, Abecassis J, Binninger I, and Birembaut P (1991). Detection of mRNAs encoding collagenase I and stromelysin 2 in carcinomas of the head and neck by in situ hybridization. Invasion Metast 11:76-83.
Purkis PE, Steel JB, Mackenzie IC, Nathrath WB, Leigh IM, and Lane EB (1990). Antibody markers of basal cells in complex epithelia. J Cell Sci 97:39-50.
Rungger-Brändle E and Gabbiani G (1983). The role of cytoskeletal and cytocontractile elements in pathologic processes. Am J Pathol 110:361-392.
Saarialho-Kere UK, Pentland AP, Birkedal-Hansen H, Parks WC, and Welgus HG (1994). Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest 94:79-88.
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, and Seiki M (1994). A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61-65.
Schmid E, Schiller DL, Grund C, Stadler J, and Franke WW (1983). Tissue type-specific expression of intermediate filament proteins in a cultured epithelial cell line from bovine mammary gland. J Cell Biol 96:37-50.
Schmid V (1978). Striated muscle: Influence of an acellular layer on the maintenance of muscle differentiation in anthomedusa. Dev Biol 64:48-59.
Sommers CL, Byers SW, Thompson EW, Torri JA, and Gelmann EP (1994). Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat 31:325-335.
Stetler-Stevenson WG, Liotta LA, and Kleiner DE Jr (1993). Extracellular matrix 6: Role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J 7:1434-1441.
SundarRaj N, Rizzo JD, Anderson SC, and Gesiotto JP (1992). Expression of vimentin by rabbit corneal epithelial cells during wound repair. Cell Tissue Res 267:347-356.
Suzuki K, Lees M, Newlands GFJ, Nagase H, and Woolley DE (1995). Activation of precursors for matrix metalloproteinases 1 (interstitial collagenase) and 3 (stromelysin) by rat mast-cell proteinase I and II. Biochem J 305:301-306.
Takeuchi S (1987). Cytochalasin B affects selectively the marginal cells of the epithelial sheet in culture. Zool Sci (Tokyo) 4:465-474.
Thompson EW, Paik S, Brünner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S, Lippman ME, Martin GR, and Dickson RB (1992). Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol 150:534-544.
Tournier J-M, Buisson A-C, Pierrot D, Zahm J-M, Birembaut P, and Puchelle E (1995). Potential role of matrix metalloproteinases in the wound repair process of the respiratory epithelium (abstract). Am J Respir Crit Care Med 151:A533.
Wagner SN, Ruhri C, Kunth K, Holecek BU, Goos M, Höfler H, and Atkinson MJ (1992). Expression of stromelysin 3 in the stromal elements of human basal cell carcinoma. Diagn Mol Pathol 1:200-205.
Werb Z (1989). Proteinases and matrix degradation. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB, editprs. Textbook of rheumatology, ed 3. Philadelphia: WB Saunders, 300-321.
Werb Z, Hembry RM, Murphy G, and Aggeler J (1986). Commitment to expression of the metalloendopeptidases, collagenase and stromelysin: Relationship of inducing events to changes in cytoskeletal architecture. J Cell Biol 102:697-702.
Woessner JF (1991). Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145-2154.
Wolf C, Chenard M-P, Durand de Grossouvre P, Bellocq J-P, Chambon P, and Basset P (1992). Breast-cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing. J Invest Dermatol 99:870-872.
Wu R, Yankaskas J, Cheng E, Knowles MR, and Boucher R (1985). Growth and differentiation of human nasal epithelial cells in culture: Serum-free, hormone-supplemented medium and proteoglycan synthesis. Am Rev Respir Dis 132:311-320.
Young PK and Grinnell F (1994). Metalloproteinase activation cascade after burn injury: A longitudinal analysis of the human wound environment. J Invest Dermatol 103:660-664.
Zahm J-M, Kaplan H, Doriot F, Pierrot D, Hérard A-L, Somelette P, and Puchelle E (in press, 1996). Cell migration and proliferation during the in vitro wound repair of the respiratory epithelium. Microsc Res Techn.
