Abstract
CD97, an epidermal growth factor (EGF)-TM7 receptor, is not restricted to hematopoetic and carcinoma cells but is also found on smooth muscle cells (SMC). We have examined its location and biochemical structure in various normal and tumorigenic SMC-containing tissues. SMC of the urinary bladder, lung bronchi and bronchioles, myometrium, and gastrointestinal tract were immunohistologically stained by using monoclonal antibodies (mabs) to the CD97 stalk region (CD97stalk). Mabs directed against an N-glycosylation-dependent epitope within the EGF-domains (CD97EGF) did not bind to normal SMC. Vascular SMC, which was also CD97EGF-negative, showed further CD97 heterogeneity. Only a few, if any, SMC from the aorta or elastic arteries of the systemic circulation were positive for CD97 mRNA and therefore also for CD97stalk. CD97stalk-positive SMC were slightly more numerous in muscular and peripheral arteries. In contrast, most venous SMC expressed CD97stalk. A comparison with other SMC molecules revealed a similar but not identical staining pattern for CD97stalk and desmin. Further CD97 heterogeneity was observed during SMC transformation. All leiomyomas (n=5) and nine out of 21 leiomyosarcomas were positive for both CD97stalk and CD97EGF. As expected, CD97EGF-positive SMC tumors expressed partly N-glycosylated CD97. Seven out of 21 leiomyosarcomas were completely devoid of CD97. Thus, CD97 showed variable expression in vascular and biochemical modification in tumorigenic SMC, suggesting that the function of the molecule is specific for the SMC subtype.
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Adams LD, Geary RL, McManus B, Schwartz SM (2000) A comparison of aorta and vena cava medial message expression by cDNA array analysis identifies a set of 68 consistently differentially expressed genes, all in aortic media. Circ Res 87:623–631
Aust G, Eichler W, Laue S, Lehmann I, Heldin N-E, Lotz O, Scherbaum WA, Dralle H, Hoang-Vu C (1997) CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res 57:1798–1806
Bjarnadottir TK, Fredriksson R, Hoglund PJ, Gloriam DE, Lagerstrom MC, Schioth HB (2004) The human and mouse gene repertoire of the adhesion family of G-protein-coupled receptors. Genomics 84:23–33
Eichler W, Aust G, Hamann D (1994) Characterization of the early activation-dependent antigen on lymphocytes defined by the monoclonal antibody BL-Ac(F2). Scand J Immunol 39:111–115
Frank ED, Warren L (1981) Aortic smooth muscle cells contain vimentin instead of desmin. Proc Natl Acad Sci USA 78:3020–3024
Frid MG, Aldashev AA, Dempsey EC, Stenmark KR (1997a) Smooth muscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ Res 81:940–952
Frid MG, Dempsey EC, Durmowicz AG, Stenmark KR (1997b) Smooth muscle cell heterogeneity in pulmonary and systemic vessels. Importance in vascular disease. Arterioscler Thromb Vasc Biol 17:1203–1209
Gabbiani G, Schmid E, Winter S, Chaponnier C, de Ckhastonay C, Vandekerckhove J, Weber K, Franke WW (1981) Vascular smooth muscle cells differ from other smooth muscle cells: predominance of vimentin filaments and a specific alpha-type actin. Proc Natl Acad Sci USA 78:298–302
Hamann J, Vogel B, Schijndel GM van, Lier RA van (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184:1185–1189
Hirschi KK, Majesky MW (2004) Smooth muscle stem cells. Anat Rec A Discov Mol Cell Evol Biol 276:22–33
Jaakkola K, Kaunismaki K, Tohka S, Yegutkin G, Vanttinen E, Havia T, Pelliniemi LJ, Virolainen M, Jalkanen S, Salmi M (1999) Human vascular adhesion protein-1 in smooth muscle cells. Am J Pathol 155:1953–1965
Jain MK, Fujita KP, Hsieh CM, Endege WO, Sibinga NE, Yet SF, Kashiki S, Lee WS, Perrella MA, Haber E, Lee ME (1996) Molecular cloning and characterization of SmLIM, a developmentally regulated LIM protein preferentially expressed in aortic smooth muscle cells. J Biol Chem 271:10194–10199
Johansson B, Eriksson A, Virtanen I, Thornell LE (1997) Intermediate filament proteins in adult human arteries. Anat Rec 247:439–448
Kowal RC, Richardson JA, Miano JM, Olson EN (1999) EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature. Circ Res 84:1166–1176
Kwakkenbos MJ, Kop EN, Stacey M, Matmati M, Gordon S, Lin HH, Hamann J (2004) The human EGF-TM7 family: a postgenomic view. Immunogenetics 55:655–666
Kwakkenbos MJ, Lier RA van, Hamann J (2002) Characterization of EGF-TM7 family members by novel monoclonal antibodies. In: Mason D (ed) Leucocyte typing VII. White cell differentiation antigens. Oxford University Press, Oxford, pp 381–383
Li L, Miano JM, Mercer B, Olson EN (1996) Expression of the SM22alpha promoter in transgenic mice provides evidence for distinct transcriptional regulatory programs in vascular and visceral smooth muscle cells. J Cell Biol 132:849–859
Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S (2004) Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J Biol Chem 279:31823–31832
Majesky MW (2003) Vascular smooth muscle diversity: insights from developmental biology. Curr Atheroscler Rep 5:208–213
Mericskay M, Parlakian A, Porteu A, Dandre F, Bonnet J, Paulin D, Li Z (2000) An overlapping CArG/octamer element is required for regulation of desmin gene transcription in arterial smooth muscle cells. Dev Biol 226:192–208
Miano JM (2003) Serum response factor: toggling between disparate programs of gene expression. J Mol Cell Cardiol 35:577–593
Moessler H, Mericskay M, Li Z, Nagl S, Paulin D, Small JV (1996) The SM 22 promoter directs tissue-specific expression in arterial but not in venous or visceral smooth muscle cells in transgenic mice. Development 122:2415–2425
Nakamura T, Ruiz-Lozano P, Lindner V, Yabe D, Taniwaki M, Furukawa Y, Kobuke K, Tashiro K, Lu Z, Andon NL, Schaub R, Matsumori A, Sasayama S, Chien KR, Honjo T (1999) DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J Biol Chem 274:22476–22483
Nanaev AK, Shirinsky VP, Birukov KG (1991) Immunofluorescent study of heterogeneity in smooth muscle cells of human fetal vessels using antibodies to myosin, desmin, and vimentin. Cell Tissue Res 266:535–540
Osborn M, Caselitz J, Weber K (1981) Heterogeneity of intermediate filament expression in vascular smooth muscle: a gradient in desmin positive cells from the rat aortic arch to the level of the arteria iliaca communis. Differentiation 20:196–202
Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84:767–801
Rao UN, Finkelstein SD, Jones MW (1999) Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas. Mod Pathol 12:1001–1009
Ren B, Yu YP, Jing L, Liu L, Michalopoulos GK, Luo JH, Rao UN (2003) Gene expression analysis of human soft tissue leiomyosarcomas. Hum Pathol 34:549–558
Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulphate glycosaminoglycans. Blood 102:2916–2924
Steinert M, Wobus M, Boltze C, Schütz A, Wahlbuhl M, Hamann J, Aust G (2002) Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues. Am J Pathol 161:1657–1667
Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG, Kelly K (2004) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counter receptors on endothelial cells. Blood 105:2836–2844
Wobus M, Vogel B, Schmücking E, Hamann J, Aust G (2004) N-glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding. Int J Cancer 112:815–822
Acknowledgements
We thank Dr. J. Neuhaus (Department of Urology, University of Leipzig) and Dr. M. Steinert (Städtisches Krankenhaus Martha-Maria Halle-Dölau, Halle, Germany) for providing bladder and lung tissues.
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This study was supported by a joint grant from the German Research Council (DFG; project AU 132/3-1) and by the Interdisziplinary Center of Clinical Research (IZKF) Leipzig at the Faculty of Medicine, University of Leipzig (project D6). E. Wandel is a fellow of the IZKF.
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Aust, G., Wandel, E., Boltze, C. et al. Diversity of CD97 in smooth muscle cells. Cell Tissue Res 324, 139–147 (2006). https://doi.org/10.1007/s00441-005-0103-2
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DOI: https://doi.org/10.1007/s00441-005-0103-2