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Dtsch Med Wochenschr 2014; 139(07): 334-338
DOI: 10.1055/s-0033-1360039
Übersicht | Review article
Onkologie, Psychosomatik
© Georg Thieme Verlag KG Stuttgart · New York

Stress und Pankreaskarzinom

β-adrenerge Signaltransduktion und TumorbiologieStress and pancreatic carcinoma – β-adrenergic signaling and tumor biology
J. Hefner
1   Schwerpunkt Psychosomatische Medizin und Psychotherapie, Medizinische Klinik und Poliklinik II, Universitätsklinik Würzburg
,
H. Csef
1   Schwerpunkt Psychosomatische Medizin und Psychotherapie, Medizinische Klinik und Poliklinik II, Universitätsklinik Würzburg
,
V. Kunzmann
2   Schwerpunkt Onkologie, Medizinische Klinik und Poliklinik II, Universitätsklinik Würzburg
› Author Affiliations
Further Information

Publication History

04 July 2013

02 October 2013

Publication Date:
04 February 2014 (online)

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Zusammenfassung

Aus Untersuchungen zu verschiedenen Karzinomen sind Regulationsmöglichkeiten der Tumorbiologie durch die β-adrenerge Signaltransduktion bekannt. Bis vor wenigen Jahren wurde das Pankreaskarzinom hierzu vergleichsweise wenig beforscht. Dabei sind neue Erkenntnisse zu Biologie und Therapieoptionen aufgrund der Inzidenz und ungünstigen Prognose gerade bei dieser Tumorentität von besonderer Bedeutung. Inzwischen beschreiben mehrere Arbeiten zum β-adrenergen System Einflüsse auf das Pankreaskarzinom in vitro und in vivo. Diese beziehen sich sowohl auf das Proliferations-und Apoptoseverhalten der Karzinomzellen als auch auf Wechselwirkungen mit dem Tumor-Microenvironment und Folgen für die Disseminations-und Metastasierungsneigung. Im Gegensatz zu anderen malignen Tumoren ergeben sich beim Pankreaskarzinom sogar Hinweise auf einen Zusammenhang zwischen β-adrenergen Signalwegen und dem Neuauftreten der Erkrankung. In der folgenden Arbeit sollen die wesentlichen Erkenntnisse zusammengefasst und Implikationen für die weitere Forschung beschrieben werden.

Abstract

In several carcinomas, β-adrenergic signaling has been found to regulate relevant processes of cancer biology. Until recently, pancreatic cancer has not been in the focus of respective research. But in view of the incidence and poor prognosis of pancreatic cancer, new insights in biology and therapeutic strategies are of prime importance. Nowadays, several reports describe influences of the catecholaminergic system on pancreatic cancer in vitro and in vivo. Effects were shown on proliferation and apoptosis of carcinoma cells as well as on interactions with tumor-microenvironment and dissemination and metastasis formation. In contrast to other entities, evidence even suggests links between β-adrenergic signaling and initiation of the disease. The following report summarizes the most relevant results demonstrating implications for further research and possible interventions.

Schlüsselwörter

Pankreaskarzinom - Katecholamine - β-Blocker - GABA - Tumor-Microenvironment

Keywords

pancreatic carcinoma - catecholamines - β-blocker - GABA - psycho-neuroimmunology
 

  • Literatur

  • 1 Al-Wadei HA, Al-Wadei MH, Schuller HM. Prevention of pancreatic cancer by the beta-blocker propranolol. Anticancer Drugs 2009; 20: 477-482
    CrossrefPubMedGoogle Scholar
  • 2 Al-Wadei HA, Ullah MF, Al-Wadei M. GABA (gamma-aminobutyric acid), a non-protein amino acid counters the beta-adrenergic cascadeactivated oncogenic signaling in pancreatic cancer: a review of experimental evidence. Mol Nutr Food Res 2011; 55: 1745-1758
    CrossrefPubMedGoogle Scholar
  • 3 Al-Wadei MH, Al-Wadei HA, Schuller HM. Pancreatic cancer cells and normal pancreatic duct epithelial cells express an autocrine catecholamine loop that is activated by nicotinic acetylcholine receptors alpha3, alpha5, and alpha7. Mol Cancer Res 2012; 10: 239-249
    CrossrefPubMedGoogle Scholar
  • 4 Almhanna K, Philip PA. Defining new paradigms for the treatment of pancreatic cancer. Curr Treat Options Oncol 2011; 12: 111-125
    CrossrefPubMedGoogle Scholar
  • 5 Antoni MH, Lutgendorf SK, Cole SW et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 2006; 6: 240-248
    Google Scholar
  • 6 Chida Y, Hamer M, Wardle J et al. Do stress-related psychosocial factors contribute to cancer incidence and survival?. Nat Clin Pract Oncol 2008; 5: 466-475
    CrossrefPubMedGoogle Scholar
  • 7 Clark KL, Loscalzo M, Trask PC et al. Psychological distress in patients with pancreatic cancer – an understudied group. Psychooncology 2010; 19: 1313-1320
    PubMedGoogle Scholar
  • 8 Cole SW, Sood AK. Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res 2012; 18: 1201-1206
    CrossrefPubMedGoogle Scholar
  • 9 Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825
    CrossrefPubMedGoogle Scholar
  • 10 Franek M, Vaculin S, Rokyta R. GABA(B) receptor agonist baclofen has non-specific antinociceptive effect in the model of peripheral neuropathy in the rat. Physiol Res 2004; 53: 351-355
    PubMedGoogle Scholar
  • 11 Gladkevich A, Korf J, Hakobyan VP et al. The peripheral GABAergic system as a target in endocrine disorders. Auton Neurosci 2006; 124: 1-8
    CrossrefPubMedGoogle Scholar
  • 12 Guo K, Ma Q, Wang L et al. Norepinephrine-induced invasion by pancreatic cancer cells is inhibited by propranolol. Oncol Rep 2009; 22: 825-830
    PubMedGoogle Scholar
  • 13 Hamer M, Chida Y, Molloy GJ. Psychological distress and cancer mortality. J Psychosom Res 2009; 66: 255-258
    CrossrefPubMedGoogle Scholar
  • 14 Hefner J, Csef H. Psychoneuroimmunologie und Krebs. Neue Ergebnisse zu psychosozialen Einflüssen auf Tumorerkrankungen. Onkologe 2011; 9: 839-850
    PubMedGoogle Scholar
  • 15 Herrmann R, Bodoky G, Ruhstaller T et al. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 2007; 25: 2212-2217
    CrossrefPubMedGoogle Scholar
  • 16 Hidalgo M. Pancreatic cancer. N Engl J Med 2010; 362: 1605-1617
    CrossrefPubMedGoogle Scholar
  • 17 Hieble JP, Bondinell WE, Ruffolo Jr RR. Alpha-and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem 1995; 38: 3415-3444
    CrossrefPubMedGoogle Scholar
  • 18 Huang XY, Wang HC, Yuan Z et al. Norepinephrine stimulates pancreatic cancer cell proliferation, migration and invasion via beta-adrenergic receptor-dependent activation of P38/MAPK pathway. Hepatogastroenterology 2012; 59: 889-893
    PubMedGoogle Scholar
  • 19 Lin X, Luo K, Lv Z et al. β-adrenoceptor action on pancreatic cancer cell proliferation and tumor growth in mice. Hepatogastroenterology 2012; 59: 584-588
    PubMedGoogle Scholar
  • 20 Lowenfels AB, Maisonneuve P. Risk factors for pancreatic cancer. J Cell Biochem 2005; 95: 649-656
    CrossrefPubMedGoogle Scholar
  • 21 Mancuso A, Calabro F, Sternberg CN. Current therapies and advances in the treatment of pancreatic cancer. Crit Rev Oncol Hematol 2006; 58: 231-241
    CrossrefPubMedGoogle Scholar
  • 22 McEwen BS. The neurobiology of stress: from serendipity to clinical relevance. Brain Res 2000; 886: 172-189
    CrossrefPubMedGoogle Scholar
  • 23 Moreno-Smith M, Lutgendorf SK, Sood AK. Impact of stress on cancer metastasis. Future Oncol 2010; 6: 1863-1881
    CrossrefPubMedGoogle Scholar
  • 24 Paez D, Labonte MJ, Lenz HJ. Pancreatic cancer: medical management (novel chemotherapeutics). Gastroenterol Clin North Am 2012; 41: 189-209
    CrossrefPubMedGoogle Scholar
  • 25 Parkin DM, Bray F, Ferlay J et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153-156
    CrossrefPubMedGoogle Scholar
  • 26 Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605-10
    CrossrefPubMedGoogle Scholar
  • 27 Reddy LH, Marque PE, Dubernet C et al. Preclinical toxicology (subacute and acute) and efficacy of a new squalenoyl gemcitabine anticancer nanomedicine. J Pharmacol Exp Ther 2008; 325: 484-90
    CrossrefPubMedGoogle Scholar
  • 28 Satin JR, Linden W, Phillips MJ. Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer 2009; 115: 5349-5361
    CrossrefPubMedGoogle Scholar
  • 29 Schuller HM, Al-Wadei HA, Majidi M. GABA B receptor is a novel drug target for pancreatic cancer. Cancer 2008; 112: 767-778
    CrossrefPubMedGoogle Scholar
  • 30 Schuller HM, Al-Wadei HA, Ullah MF et al. Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis 2012; 33: 191-196
    CrossrefPubMedGoogle Scholar
  • 31 Shan T, Ma Q, Zhang D et al. β2-adrenoceptor blocker synergizes with gemcitabine to inhibit the proliferation of pancreatic cancer cells via apoptosis induction. Eur J Pharmacol 2011; 665: 1-7
    CrossrefPubMedGoogle Scholar
  • 32 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30
    CrossrefPubMedGoogle Scholar
  • 33 Spiegel D, Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry 2003; 54: 269-282
    CrossrefPubMedGoogle Scholar
  • 34 Thaker PH, Han LY, Kamat AA et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 2006; 12: 939-944
    Google Scholar
  • 35 Thaker PH, Lutgendorf SK, Sood AK. The neuroendocrine impact of chronic stress on cancer. Cell Cycle 2007; 6: 430-433
    CrossrefPubMedGoogle Scholar
  • 36 Troiani T, Martinelli E, Capasso A et al. Targeting EGFR in pancreatic cancer treatment. Curr Drug Targets 2012; 13: 802-810
    CrossrefPubMedGoogle Scholar
  • 37 Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002; 53: 865-871
    CrossrefPubMedGoogle Scholar
  • 38 Wadler S. Molecular targeting in pancreatic cancer. Rev Recent Clin Trials 2007; 2: 69-75
    CrossrefPubMedGoogle Scholar
  • 39 Weddle DL, Tithoff P, Williams M et al. Beta-adrenergic growth regulation of human cancer cell lines derived from pancreatic ductal carcinomas. Carcinogenesis 2001; 22: 473-479
    CrossrefPubMedGoogle Scholar
  • 40 Zabora J, BrintzenhofeSzoc K, Curbow B et al. The prevalence of psychological distress by cancer site. Psychooncology 2001; 10: 19-28
    CrossrefPubMedGoogle Scholar
  • 41 Zhang D, Ma Q, Shen S et al. Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: the study of beta-adrenoceptor antagonist's anticancer effect in pancreatic cancer cell. Pancreas 2009; 38: 94-100
    CrossrefPubMedGoogle Scholar
  • 42 Zhang D, Ma QY, Hu HT et al. β2-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NFkappaB and AP-1. Cancer Biol Ther 2010; 10: 19-29
    CrossrefPubMedGoogle Scholar
  • 43 Zhang D, Ma Q, Wang Z et al. β2-adrenoceptor blockage induces G1/S phase arrest and apoptosis in pancreatic cancer cells via Ras/Akt/NFkappaB pathway. Mol Cancer 2011; 10: 146
    CrossrefPubMedGoogle Scholar