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CD44 and tenascin play critical roles in growth and vascular development of the chick chorioallantoic membrane and are targets of cigarette smoke

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Abstract

Chorioallantoic membranes (CAMs) were used to determine which extracellular matrix molecules play essential roles in growth and vascular development in vivo and whether expression of critical molecules is affected by cigarette smoke exposure. Treatment of CAMs on day 5 of development with antibodies to CD44 or tenascin, but not to other matrix molecules, inhibited CAM growth and affected various aspects of blood vessel development including normal growth and branching of vessels, migration of vessels, and formation and differentiation of the capillary plexus. DNA synthesis was inhibited by antibodies to both C44 and tenascin which probably accounted for many of the phenotypic changes observed in treated CAMs. CD44 was located on all cells in day 5 CAMs, and tenascin, while present throughout the CAM, was especially abundant around large, non-migratory mesodermal blood vessels and endodermal cells that were positioned away from the direction of blood vessel migration. These data suggest that while tenascin is required for normal blood vessel migration, high levels of tenascin inhibit migration. The different distributions of CD44 and tenascin in CAMs and the observation that antibodies to either CD44 or tenascin produced similar phenotypes indicate that CD44 and tenascin were not functionally redundant. Mainstream smoke solutions, which produce a phenotype similar to that seen with anti-tenascin and anti-CD44, inhibited expression of CD44 mRNA and increased tenascin mRNA expression. 3-Ethylpyridine, a chemical in cigarette smoke that produced changes in CAM development similar to anti-CD44 and anti-tenascin treatment, also increased tenascin mRNA expression, but did not affect CD44. Together these data show that tenascin and CD44 play critical roles in early growth and vascular development of the CAM and support the idea that 3-ethylpyridine in mainstream smoke impairs CAM growth and vascular development by targeting expression of tenascin. 3-Ethylpyridine is generally regarded as safe and is used in many consumer products including food and tobacco.

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References

  • Ahrens T, Assmann V, Fieber C, Termeer C, Herrlich P, Hofmann M, Simon JC (2001) CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation. J Invest Dermatol 116:93–101

    Article  CAS  PubMed  Google Scholar 

  • Augustin HG, Braun K, Telemenkis I, Modlich U, Kuhn W (1995) Ovarian angiogenesis. Am J Pathol 147:339–350

    CAS  PubMed  Google Scholar 

  • Ausprunk DH (1986) Distribution of hyaluronic acid and sulfated glycosaminoglycans during blood-vessel development in the chick chorioallantoic membrane. Am J Anat 177:313–331

    CAS  PubMed  Google Scholar 

  • Ausprunk DH, Dethlefsen SM, Higgins ER (1991) Distribution of fibronectin, laminin, type IV collagen during development of blood vessels in the chick chorioallantoic membrane. In: Feinberg RN, Sherer GK, Auerbach R (eds)The development of the vascular system, vol. 14. Karger, Basel pp 93–108

  • Birch M, Mitchell S, Hart IR (1991) Isolation and characterization of human melanoma cell variants expressing high and low levels of CD44. Cancer Res 51:6660–6667

    CAS  PubMed  Google Scholar 

  • Bronner-Fraser M. (1988) Distribution and function of tenascin during cranial neural crest development in the chick. JNeuro Res 21:135–147

    CAS  Google Scholar 

  • Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nature 6:389–395

    Article  CAS  Google Scholar 

  • Chuong CM, Chen HM (1991) Enhanced expression of neural cell adhesion molecules and tenascin (cytotactin) during wound healing. Am JPathol 138:427–440

    CAS  Google Scholar 

  • DeFouw DO, Rizzo VJ, Steinfeld R, Feinberg RN (1989) Mapping of the microcirculation in the chick chorioallantoic membrane during normal angiogenesis. MicrovasRes 38:136–147

    CAS  Google Scholar 

  • End P, Panayotou G, Entwistle A, Waterfield MD, Chiquet M (1992). Tenascin: a modulator of cell growth. Eur J Biochem 209:1041–1051

    CAS  PubMed  Google Scholar 

  • Faassen A., Schrager JA, Klein DJ, Oegema TR, Couchman JR, McCarthy JB (1992) A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol 116:521–531

    CAS  PubMed  Google Scholar 

  • Findlay JK (1986) Angiogenesis in reproductive tissues. J Endocrinol 111:357–366

    CAS  PubMed  Google Scholar 

  • Flamme I, Frolich T, Risau W (1997) Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 173:206–210

    Article  CAS  PubMed  Google Scholar 

  • Folkman J (1996) Fighting cancer by attacking its blood supply. Sci Am 275:150–154

    CAS  PubMed  Google Scholar 

  • Folkman J, Shing J (1992) Angiogenesis. J Biol Chem 267:10931–10934

    CAS  PubMed  Google Scholar 

  • Frick WG, Seals RR Jr (1994) Smoking and wound healing: a review. Tex Dent J 111:21–23

    CAS  Google Scholar 

  • Garcion E, Faissner A, ffrench-Constant C (2001) Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. Development 128:2485–2496

    CAS  PubMed  Google Scholar 

  • Goussia AC, Ioachim EE. Peschos D, Assimakopoulos DA, Skevas A, Agnantis NJ (2000) Expression of the extracellular matrix protein tenascin in laryngeal epithelial lesions: correlation with fibronectin, CD44, cathepsin D and proliferation indices. Virchows Arch 436:579–584

    CAS  PubMed  Google Scholar 

  • Hamilton HL (1965) Lillie’s Development of the chick. Holt, Rinehart, and Winston, New York

  • Ikuta T, Ariga H, Matsumoto K (2000) Extracellular matrix tenascin-X in combination with vascular endothelial growth factor B enhances endothelial cell proliferation. Genes Cells 5:913–927

    CAS  PubMed  Google Scholar 

  • Jallo GI, Friedlander DR, Kelly PJ, Wisoff JH, Grumet M, Zagzag D (1997) Tenascin-C expression in the cyst wall and fluid of human brain tumors correlates with angiogenesis. Neurosurgery 41:1052–1059

    CAS  PubMed  Google Scholar 

  • Ji L, Melkonian G, Riveles K, Talbot P (2002) Identification of pyridine compounds in cigarette smoke solution that inhibit growth of the chick chorioallantoic membrane. Toxicol Sci 69:217–225

    Article  CAS  PubMed  Google Scholar 

  • Jones FS, Jones PL (2000) The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 218:235–259

    CAS  PubMed  Google Scholar 

  • Jones PL, Cowan KN, Rabinovitch M (1997) Tenascin-C, proliferation and subendothelial fibronectin in progressive pulmonary vascular disease. Am J Pathol 150:1349–1360

    CAS  PubMed  Google Scholar 

  • Kaya G, Rodriguez I, Jorcano JL, Vassalli P, Stamenkovic I (1997) Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation. Genes Dev 11:996–1007

    CAS  PubMed  Google Scholar 

  • Knoll M, Talbot P (1998) Cigarette smoke inhibits oocyte cumulus complex pick-up by the oviduct independent of ciliary beat frequency. Reprod Toxicol 12:57–68

    Article  CAS  PubMed  Google Scholar 

  • Kornowski R, Fuchs S, Leon MB, Epstein SE (2000) Delivery strategies to achieve therapeutic myocardial angiogenesis. Circulation 101:454–458

    CAS  PubMed  Google Scholar 

  • Krushel LA, Prieto AL, Edelman GM, Crossin KL (1994) Differential effects of cytotactin/tenascin fusion proteins on intracellular pH and cell morphology. J Cell Physiol 161:508–518

    CAS  PubMed  Google Scholar 

  • Li J, Zhang YP, Kirsner RS (2003) Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 60:107–114

    Article  CAS  PubMed  Google Scholar 

  • Lokeshwar VB, Iida N, Bourguignon LY (1996) The cell adhesion molecule, GP116, is a new CD44 variant (ex14/v10) involved in hyaluronic acid binding and endothelial cell proliferation. J Biol Chem 271:23853–23864

    Article  CAS  PubMed  Google Scholar 

  • Lokeshwar VB, Selzer MG (2000) Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells. J Biol Chem 275:27641–27649

    CAS  PubMed  Google Scholar 

  • Ma L, Chow JY, Cho CH (1999) Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach. Am J Physiol 276:G238–248

    CAS  PubMed  Google Scholar 

  • Mackie EJ, Halfter W, Liverani D (1988) Induction of tenascin in healing wounds. J Cell Biol 107:2757–2767

    CAS  PubMed  Google Scholar 

  • Magers T, Talbot P, DiCarlantonio G, Knoll M, Demers D, Tsai I, Hoodbhoy T (1995) Cigarette smoke inhalation affects the reproductive system of female hamsters. Reprod Toxicol 9:513–525

    Article  CAS  PubMed  Google Scholar 

  • Martin TR, Bracken MB (1986) Association of low birth weight with passive smoke exposure in pregnancy. Am J Epidemiol 124:633–642

    CAS  PubMed  Google Scholar 

  • Martins-Green M, Hanafusa H (1997) The 9E3/CEF4 gene and its product the chicken chemotactic and angiogenic factor (cCAF): potential roles in wound healing and tumor development. Cytokine Growth Factor Rev 8:221–232

    Article  CAS  PubMed  Google Scholar 

  • Melkonian G, Cheung L, Marr R, Tong C, Talbot P (2002) Mainstream and sidestream cigarette smoke inhibit growth and angiogenesis in the day 5 chick chorioallantoic membrane. Toxicol Sci 68:237–248

    Article  CAS  PubMed  Google Scholar 

  • Melkonian G, Le C, Zheng W, Talbot P, Martins-Green M (2000) Normal patterns of angiogenesis and extracellular matrix deposition in chick chorioallantoic membranes are disrupted by mainstream and sidestream cigarette smoke. Tox Applied Pharm 163:26–37

    Article  CAS  Google Scholar 

  • Melkonian G, Munoz N, Chung J, Tong C, Marr R, Talbot P (2001) Capillary plexus development in the day 5 - day 6 chick chorioallantoic membrane is inhibited by Cytochalasin D and Suramin. J Exp Zool 292:241–254

    Article  Google Scholar 

  • Nandi A, Estess P, Siegelman MH (2000) Hyaluronan anchoring and regulation on the surface of vascular endothelial cells is mediated through the functionally active form of CD44. J Biol Chem 275:14939–14948

    Article  CAS  PubMed  Google Scholar 

  • Nico B, Vacca A, De Giorgis M, Roncali L, Ribatti D (2001) Vascular endothelial growth factor and vascular endothelial growth factor receptor-2 expression in the chick embryo area vasculosa. Histochem J 33:283–286

    Article  CAS  PubMed  Google Scholar 

  • Oz B, Karayel FA, Gazio NL, Ozlen F, Balci K (2000) The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas. Pathol Oncol Res 6:118–124

    CAS  PubMed  Google Scholar 

  • Pilarski LM, Pruski E, Wizniak J, Paine D, Seeberger K, Mant MJ, Brown CB, Belch AR (1999). Potential role for hyaluronan and the hyaluronan receptor RHAMM in mobilization and trafficking of hematopoietic progenitor cells. Blood 93:2918–2927

    CAS  PubMed  Google Scholar 

  • Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4:33–45

    Article  CAS  PubMed  Google Scholar 

  • Rabinovitch M (1999) EVE and beyond, retro and prospective insights. Am J Physiol 277:L5–12

    CAS  PubMed  Google Scholar 

  • Rahmanian M, Heldin P (2002) Testicular hyaluronidase induces tubular structures of endothelial cells grown in three-dimensional collagen gel through a CD44-mediated mechanism. Int J Cancer 97:601–607

    Article  CAS  PubMed  Google Scholar 

  • Raines EW (2000). The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 81:173–182

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Bertossi M, Nico B, Vacca A, Ria R, Riva A, Roncali L, Presta M (1998A) Role of basic fibroblast growth factor in the formation of the capillary plexus in the chick embryo chorioallantoic membrane. An in situ hybridization, immunohistochemical and ultrastructural study. J Submicrosc Cytol Pathol 30:127–136

    CAS  PubMed  Google Scholar 

  • Ribatti D, Loverro G, Vacca A, Greco P, Roncali L, Selvaggi L (1998B) Expression of tenascin is related to angiogenesis in pre-eclampsia. Eur J Clin Invest 28:373–378

    Article  CAS  PubMed  Google Scholar 

  • Ribatti D, Vacca A (1999) Models for studying angiogenesis in vivo. Int J Biol Markers 14:207–213

    CAS  PubMed  Google Scholar 

  • Ribatti D, Vacca A, Roncali L, Dammacco F (1996) The chick chorioallantoic membrane as a model for in vivo research on angiogenesis. Int J Dev Biol 40:1189–1197

    CAS  PubMed  Google Scholar 

  • Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674

    CAS  PubMed  Google Scholar 

  • Rosengart TK, Lee LY, Patel SR, Sanborn TA, Parikh M, Bergman GW, Hachamovitch R, Szulc M, Kligfield PD, Okin, PM et al (1999) Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 100:468–474

    Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

    Google Scholar 

  • Savani RC, Cao G, Pooler PM, Zaman A, Zhou Z, DeLisser HM (2001) Differential involvement of the hyaluronan receptors CD44 and RHAMM in endothelial cell function and angiogenesis. J Biol Chemi 276(39):36770–36778

    Article  CAS  Google Scholar 

  • Sherman L, Wainwright D, Ponta H, Herrlich P (1998) A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth. Genes Dev 12:1058–1071

    CAS  PubMed  Google Scholar 

  • Silverstein P (1992) Smoking and wound healing. Am J Med 93(1A):22S–24S

    CAS  PubMed  Google Scholar 

  • Stillman RJ, Rosenberg MJ, Sachs BP (1986) Smoking and reproduction. Fertil Steril 46:545–566

    CAS  PubMed  Google Scholar 

  • Su TT (2000) The regulation of cell growth and proliferation during organogenesis. In Vivo 14:141–148

    CAS  PubMed  Google Scholar 

  • Talbot P, DiCarlantonio G, Knoll M (1998) Identification of cigarette smoke components that alter functioning of hamster (Mesocricetus auratus) oviducts in vitro. Biol Reprod 58:1047–1053

    CAS  PubMed  Google Scholar 

  • Thomas L, Byers HR, Vink J, Stamenkovic I (1992) CD44H regulates tumor cell migration on hyaluronate-coated substrate. J Cell Biol 118:971–977

    PubMed  Google Scholar 

  • Tokes AM, Hortovanyi E, Kulka J, Jackel M, Kerenyi T, Kadar A (1999) Tenascin expression and angiogenesis in breast cancers. Pathol Res Pract 195:821–828

    CAS  PubMed  Google Scholar 

  • Tourmaa TE (1995) The adverse effects of tobacco smoking on reproduction and health: a review from the literature. Nutr Health 10:105–120

    PubMed  Google Scholar 

  • Trochon V, Mabilat C, Bertrand P, Legrand Y, Smadja-Joffe F, Soria C, Delpech B, Lu H (1996) Evidence of involvement of CD44 in endothelial cell proliferation, migration and angiogenesis in vitro. Int J Cancer 66:664–668

    Article  CAS  PubMed  Google Scholar 

  • Tucker RP (2001) Abnormal neural crest cell migration after the in vivo knockdown of tenascin-C expression with morpholino antisense oligonucleotides. Dev Dyn 222:115–119

    Article  CAS  PubMed  Google Scholar 

  • Weinstein BM (1999) What guides early embryonic blood vessel formation? Dev Dyn 215:2–11

    PubMed  Google Scholar 

  • Wilting J, Brand-Saberi,B, Kurz H, Christ B (1995) Development of the embryonic vascular system. Cell Mol Biol Res 41:219–232

    CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Gene Huh for allowing us to use his gel documentation system and Karen Riveles for her helpful suggestions on the manuscript. Supported by a grant from the California Tobacco Related Disease Research Program.

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  1. Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA

    G. Melkonian, J. L. Wang, J. Chung, N. Munoz & P. Talbot

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  1. G. Melkonian
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  2. J. L. Wang
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  3. J. Chung
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  4. N. Munoz
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  5. P. Talbot
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Correspondence to P. Talbot.

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Melkonian, G., Wang, J.L., Chung, J. et al. CD44 and tenascin play critical roles in growth and vascular development of the chick chorioallantoic membrane and are targets of cigarette smoke. Anat Embryol 208, 109–120 (2004). https://doi.org/10.1007/s00429-003-0376-8

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