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Immunolocalization of substance P and NK-1 receptor in vascular anomalies

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Abstract

The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also ubiquitous in the human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates tumoral angiogenesis and proliferation. Thus, knowledge of this system is the key for a better understanding and, hence, a better management of many human diseases, including vascular anomalies (VA). This study aims to examine the expression and localization of both SP and the NK-1 receptor in different vascular anomalies using an immunohistochemical technique. Our results demonstrated predominantly nuclear localization of SP in venous malformations and in one haemangioma sample, in contrast with cytoplasmic expression in capillary malformations and rapidly involuting congenital hemangioma (RICH). NK-1 receptor showed a cytoplasmic localization in all VA. In summary, all these findings demonstrate that SP and NK-1 receptor are expressed in VA, with different expression patterns depending on the nature of the anomaly, suggesting that they could play an important role in the pathogenesis of VA.

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References

  1. Aliakbari J, Sreedharan SP, Turck CW et al (1987) Selective localization of vasoactive intestinal peptide and substance P in human eosinophils. Biochem Biophys Res Commun 148:1440–1445

    Article  CAS  PubMed  Google Scholar 

  2. Berger M, Neth O, Ilmer M et al (2014) Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo. J Hepatol 60:985–994

    Article  CAS  PubMed  Google Scholar 

  3. Bielenberg DR, Bucana CD, Sanchez R et al (1999) Progressive growth of infantile cutaneous hemangiomas is directly correlated with hyperplasia and angiogenesis of adjacent epidermis and inversely correlated with expression of the endogenous angiogenesis inhibitor, IFN-beta. Int J Oncol 14:401–408

    CAS  PubMed  Google Scholar 

  4. Böckle BC, Sölder E, Kind S et al (2008) DC-SIGN + CD163 + Macrophages Expressing Hyaluronan Receptor LYVE-1 Are Located within Chorion Villi of the Placenta. Placenta 29:187–192

    Article  PubMed  Google Scholar 

  5. Boscolo E, Bischoff J (2009) Vasculogenesis in infantile hemangioma. Angiogenesis 12:197–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Brener S, González-Moles MA, Tostes D et al (2009) A role for the substance P/NK-1 receptor complex in cell proliferation in oral squamous cell carcinoma. Anticancer Res 29:2323–2329

    PubMed  Google Scholar 

  7. Castellani ML, Galzio RJ, Felaco P et al (2010) VEGF, substance P and stress, new aspects: a revisited study. J Biol Regul Homeost Agents 24(3):229–237

    CAS  PubMed  Google Scholar 

  8. Chiwakata C, Brackmann B, Hunt N et al (1991) Tachykinin (substance-P) gene expression in Leydig cells of the human and mouse testis. Endocrinology 128:2441–2448

    Article  CAS  PubMed  Google Scholar 

  9. Demir R, Seval Y, Huppertz B (2007) Vasculogenesis and angiogenesis in the early human placenta. Acta Histochem 109:257–265

    Article  CAS  PubMed  Google Scholar 

  10. Esteban F, González-Moles MA, Castro D et al (2009) Expression of substance P and neurokinin-1-receptor in laryngeal cancer: linking chronic inflammation to cancer promotion and progression. Histopathology 54:258–260

    Article  PubMed  Google Scholar 

  11. Garzon MC, Huang JT, Enjolras O et al (2007) Vascular malformations: Part II: associated syndromes. J Am Acad Dermatol 56:541–564

    Article  PubMed  Google Scholar 

  12. González-Moles MA, Mosqueda-Taylor A, Esteban F et al (2008) Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours. Oral Oncol 44:1127–1133

    Article  PubMed  Google Scholar 

  13. Guha S, Eibl G, Kisfalvi K et al (2005) Broad-spectrum G protein–coupled receptor antagonist, [D-Arg1, DTrp5,7,9, Leu11]SP: a dual inhibitor of growth and angiogenesis in pancreatic cancer. Cancer Res 65:2738–2745

    Article  CAS  PubMed  Google Scholar 

  14. Hennig IM, Laissue JA, Horisberger U et al (1995) Substance-P receptors in human primary neoplasms: tumoral and vascular localization. Int J Cancer 61:786–792

    Article  CAS  PubMed  Google Scholar 

  15. International Society for the Study of Vascular Anomalies (2014) ISSVA Classification of vascular anomalies. In: Classification. International Society for the Study of Vascular Anomalies. www.issva.org/classification. Accessed Apr 2014

  16. Jang JH, Nam TS, Paik KS et al (2004) Involvement of peripherally released substance P and calcitonin gene-related peptide in mediating mechanical hyperalgesia in a traumaticneuropathy model of the rat. Neurosci Lett 360:129–132

    Article  CAS  PubMed  Google Scholar 

  17. Koh YH, Tamizhselvi R, Bhatia M (2010) Extracellular signalregulated kinase 1/2 and c-Jun NH2-terminal kinase, through nuclear factor-kappaB and activator protein-1, contribute to caerulein-induced expression of substance P and neurokinin-1 receptors in pancreatic acinar cells. J Pharmacol Exp Ther 332:940–948

    Article  CAS  PubMed  Google Scholar 

  18. Lai JP, Douglas SD, Ho WZ (1998) Human lymphocytes express substance P and its receptor. J Neuroimmunol 86:80–86

    Article  CAS  PubMed  Google Scholar 

  19. Linnik MD, Moskowitz MA (1989) Identification of immunoreactive substance P in human and other mammalian endothelial cells. Peptides 10:957–962

    Article  CAS  PubMed  Google Scholar 

  20. Luo W, Sharif TR, Sharif M (1996) Substance P-induced mitogenesis in human astrocytoma cells correlates with activation of the mitogen-activated protein kinase signaling pathway. Cancer Res 56:4983–4991

    CAS  PubMed  Google Scholar 

  21. Milner P, Kirkpatrick KA, Ralevic V et al (1990) Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow. Proc Biol Sci 241:245–248

    Article  CAS  PubMed  Google Scholar 

  22. Muñoz M, Bernabeu-Wittel J, Coveñas R (2011) NK-1 as a melanoma target. Expert Opinion Therapeutic Targets 15:889–897

    Article  Google Scholar 

  23. Muñoz M, Carranza A, Pavón A et al (2013) Immunolocalization of substance P and NK-1 receptor in hofbauer cells in human normal placenta. Microsc Res Tech 76:1310–1313

    Article  PubMed  Google Scholar 

  24. Muñoz M, Coveñas R (2010) A new frontier in the treatment of cancer: NK-1 receptor antagonists. Curr Med Chem 17:504–516

    Article  PubMed  Google Scholar 

  25. Muñoz M, Coveñas R (2011) NK-1 receptor antagonists: a new paradigm in pharmacological therapy. Curr Med Chem 18:1820–1831

    Article  PubMed  Google Scholar 

  26. Muñoz M, Coveñas R (2013) Involvement of substance P and the NK-1 receptor in cancer. Peptides 48:1–9

    Article  PubMed  Google Scholar 

  27. Muñoz M, Coveñas R, Esteban F et al (2015) The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs. J Biosci 40:441–463

    Article  PubMed  Google Scholar 

  28. Muñoz M, González-Ortega A, Rosso M et al (2012) The substance P/Neurokinin-1 receptor system in lung cancer: focus on the antitumor action of neurokinin-1 receptor antagonists. Peptides 38:318–325

    Article  PubMed  Google Scholar 

  29. Muñoz M, Pavon A, Rosso M et al (2010) Immunolocalization of NK-1 receptor and substance P in human normal placenta. Placenta 31:649–651

    Article  PubMed  Google Scholar 

  30. North PE, Waner M, Mizeracki A et al (2000) GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol 31:11–22

    Article  CAS  PubMed  Google Scholar 

  31. North PE, Waner M, Mizeracki A et al (2001) A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol 137:559–570

    Article  CAS  PubMed  Google Scholar 

  32. Samsam M, Coveñas R, Csillik B et al (2001) Depletion of substance P, neurokinin A and calcitonin gene-related peptide from the contralateral and ipsilateral caudal trigeminal nucleus following unilateral electrical stimulation of the trigeminal ganglion; A possible neurophysiological and neuroanatomical link to generalized head pain. J Chem Neuroanat 21:161–169

    Article  CAS  PubMed  Google Scholar 

  33. Walczak-Drzewiecka A, Ratajewski M, Wagner W et al (2008) HIF1alphais up-regulated in activated mast cells by a process that involves calcineurin and NFAT. J Immunol 181:1665–1672

    Article  CAS  PubMed  Google Scholar 

  34. Wassef M, Blei F, Adams D et al (2015) Vascular anomalies classification: recommendations from the International Society for the Study of Vascular Anomalies. Pediatrics 136:203–214

    Article  Google Scholar 

  35. Ziche M, Morbidelli L, Pacini M et al (1990) Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. Microvasc Res 40:264–278

    Article  CAS  PubMed  Google Scholar 

  36. Ziche M, Morbidelli L, Pacini M et al (1994) Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 94:2036–2044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research has been conducted using samples from the HUVR-IBIS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT13/0010/0056). The authors thank the donors and the HUVR-IBiS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT13/0010/0056) for the human specimens used in this study and Mr. Francisco Jesus Fuentes for technical assistance.

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Authors and Affiliations

  1. Department of Dermatology, Virgen del Rocio University Hospital, Seville, Spain

    Alejandro Ortiz-Prieto, José Bernabeu-Wittel & Ana I. Lorente-Lavirgen

  2. Department of Pathology, Virgen del Rocio University Hospital, Seville, Spain

    Teresa Zulueta-Dorado

  3. Research Laboratory on Neuropeptides, Biomedicine Institute, Virgen del Rocio, University Hospital, Avda. Manuel Siurot s/n, 41013, Seville, Spain

    Miguel Muñoz

Authors
  1. Alejandro Ortiz-Prieto
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  2. José Bernabeu-Wittel
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  3. Teresa Zulueta-Dorado
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  4. Ana I. Lorente-Lavirgen
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  5. Miguel Muñoz
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Correspondence to Miguel Muñoz.

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Informed consent was obtained from all individual participants included in the study.

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Ortiz-Prieto, A., Bernabeu-Wittel, J., Zulueta-Dorado, T. et al. Immunolocalization of substance P and NK-1 receptor in vascular anomalies. Arch Dermatol Res 309, 97–102 (2017). https://doi.org/10.1007/s00403-016-1707-y

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  • DOI: https://doi.org/10.1007/s00403-016-1707-y

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