Cancer: Stress and PAI-1
Received Date: Feb 18, 2019 / Accepted Date: Apr 18, 2019 / Published Date: Apr 25, 2019
Cancer is a group of diseases that are characterized by the development of abnormal cells, which divide almost without limit, develop, spread without control anywhere in the body, losing the cells their ability to disappear by an anti- apoptotic action, essential process for malignant transformation and tumor development. The onset and development of cancer is associated with multiple causes and predisposing factors such as stress and psychosocial factors PAI-1 is a gene regulated by stress and is paradoxicallyinteracted in close relation with uPA in the development of tumors.
Keywords: Cancer; Tumors; Genomic; Stress; Medicine
The main cause of death of patients suffering from cancer is the presence of metastasis, a complex process that leads to the survival and growth of unique subpopulations located in areas more or less distant from their primary tumor, this being related to the problem of resistance to habitual therapy in many cases [1-3]. Cancer research over the years has shown that it is a genetic disease, not always hereditary, whose expression of cellular genomic damage lies virtually in all cells of different tissues in humans and animals [4-7]. Oncogenic mutations, as a consequence of a genetic instability, leads to an accumulation of mutations of the gene, causing the initiation of the tumor and its progression [8,9]. This process of initiation and development of cancer is associated with multiple causes and predisposing factors such as viruses, chemical mutagen, radiation, stress and psychosocial factors .
Cancer and stress have historically been related to medicine. Galen (130-210 B.C.) in his study "DeTumoribus" indicates that women who express melancholy was more susceptible to cancer . In this line, the presence of chronic alarms or emotional stressors such as depressions, fear, anxiety is observed with certain frequency in patients affected by cancer, finding among the most frequent [12-14]. Chronic stress stimulates the hypothalamic-pituitary-adrenal (HPA) -axis systems, with the release of glucocorticoids (cortisone in humans), and the sympathetic nervous system that regulates catecholamine levels (adrenaline noradrenaline), as the most important hormones in stress, and the regulation of the inflammatory response through immune cells . In the same way, chronic stress favors tumor development, increased expression of metalloproteinase of the extracellular matrix and endothelial vascular growth factor, caused high levels of catecholamines and greater tumor progression activity . However, some studies find little relationship between cancer risk and stress levels [16,17].
Oxidative stress, the product of a cluster of reactive oxygen species/ reactive nitrogen species, as a consequence of endogenous or exogenous stressors, is present in many cancer cells, generating a cellular redox disequilibrium that may be related to a stimulation oncogenic, which generates DNA mutations, critical stage and strongly inherent to the etiology of cancer [18,19]. Currently there are findings that show that cellular and molecular responses to the action of stress are related to the development of cancer progression and metastasis .
The acute experimental stress (survival of the animal between 1 and 4 days), after the administration of endotoxin at minimum lethal doses as a stressor, causes changes in the anatomical structure and function, leading to a marked increase of expression of the Plasminogen Activator Inhibitor (PAI-1) main inhibitor of the urokinase-type activator (uPA) and possible cause of the high frequency of vascular infarcts in different organs, including the HPA axis [21-24]. PAI-1 is a gene regulated by stress and is paradoxically interacted in close relation with uPA in the development of tumors . The plasminogen system components uPA, PAI-1 are promoters in tumor growth, in invasion and metastasis, for their action on angiogenesis and cell migration and are found in high concentration in cancer cells and in plasma samples [26-31]. There is convincing clinical evidence that PAI-1 is a key factor for the invasion of tumors and metastasis [32,33]. Both the activation system (uPA) and the inhibition of the plasminogen mechanism (PAI- 1) are overexpressed in many cancerous processes and are considered an indicator of poor prognosis in patients with cancer [33-39]. All the studies indicated lead to the conclusion that PAI-inhibitors could represent a field with therapeutic possibilities [40-42].
Cancer is a very broad field within human pathology, constituting a frequent process with a high incidence of mortality. The onset and development of cancer is associated with multiple causes and predisposing factors such as stress and psychosocial factors, stressors that are very studied at present due to their social importance. Both the activation system (uPA) and the inhibition of the plasminogen mechanism (PAI-1) are overexpressed in many cancerous processes and are considered an unfavorable prognostic indicator for patients with cancer. PAI-1 is a gene regulated by stress and is paradoxically interacted in close relation with uPA in the development of tumors. All the studies indicated lead to the conclusion that PAI-1 inhibitors represent a field with therapeutic possibilities.
- Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57-70.
- Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anti-cancer chemotherapy. Oncogene 25: 4798-4811.
- Fulda S (2010) Evasion of apoptosis as a cellular stress response in cancer. Int J Cell Biol 2010:1-6.
- Harris CC (1991) Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 51: 5023S-5044S.
- Chene G, Lamblin G, Le Ball-Carval K, Beaufils E, Chabert P, et al. (2016) Lucy's cancer(s): A prehistorical origin? Gynecol Obstet Fertil 44: 690-700.
- Cullen JM, Page R, Misdrop W (2002) An overview of cancer pathogenesis, diagnosis and management. In: Tumor in Domestic Animals. (4th edn), Iowa State Press, Ames, IA, USA.
- Lowe SW, Cepero E, Evan G (2004) Intrinsic tumour suppression. Nature 432: 307-315.
- Lengauer C, Kinzler KW, Volgelstein B (1997) Genetic instability in colorectal cancers. Nature 386: 623-627.
- Halazonetis TD, Gorgoulis VG, Bartek J (2008) An oncogene-induced DNA damage model for cancer development. Science 319: 1352-1355.
- Powel N D, Tarr AJ, Sheridan J E (2013) Psychosocial stress and inflammation in cancer. Brain Behav Immun 30: S41-S47.
- Rosch PJ (1979) Stress and cancer: A disease of adaptation? In: Cancer, Stress, and Death. Sloan-Kettering Institute Cancer Series. Springer, Boston, MA, USA.
- Spiegel D, Bloom JR, Kraemer HC, Gottheil E (1989) Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2: 888-891.
- Williams JB, Pang D, Delgado B, Kocherginsky M, Tretiakova M, et al. (2009) A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation. Cancer Prev Res 2: 850-861.
- Cui B, Luo Y, Tian P, Peng F, Lu J, et al. (2019) Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem- like cells. J Clin Invest 129: 1030-1046.
- Xie H, Li C, He Y, Griffin R, Ye Q, et al. (2015) Chronic stress promotes oral cancer growth and angiogenesis with increased circulating catecholamine and glucocorticoid levels in a mouse model. Oral Oncol 51: 991-997.
- Ross K (2008) Mapping pathways from stress to cancer progression. J Natl Cancer Institute 100: 914-917.
- Schoemaker MJ, Jones ME, Wright LB, Griffin J, McFadden E, et al. (2016) Psychological stress, adverse life events breast cancer incidence: A cohort investigation in 106,000 women in the United Kingdom. Breast Cancer Res 18: 72.
- Toyokuni S, Okamoto K, Yodoi J, Hiai H (1995) Persistent oxidative stress in cancer. FEBS Letters 358: 1-3.
- Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160: 1-40.
- Moreno-Smith M, Lutgendorf SK, Sood AK (2010) Impact of stress on cancer metastasis. Future Oncol 6: 1863-1881.
- Lasierra-Cirujeda J (1968) Contributions to the vascular distribution and topography neurosecretora in the surface of contacto hipofisaria, as well as, concomitant visceral vascularizaciones in connection with experimental states of alarm. Ann of Anat 17: 485-536.
- Colucci M, Paramo JA, Collen D (1985) Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 75: 818-824.
- Quax PH, Van den Hoogen CM, Werheijen JH, Padro T, Zeheb R, et al, (1990) Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. J Biol Chem 265: 15560-15563.
- Yamamoto K, Loskutoff DJ (1996) Fibrin deposition in tissue from endotoxin- treated mice correlates with decreases in the expression of -type but not tissue- type plasminogen activator. J Clin Invest 97: 2440-2451.
- Yamamoto K, Takeshita K, Shimokawa T, Yi H, Isobe K, et al. (2002). Plasminogen activator inhibitor-1 is a major stress-regulated gene: Implications for stress-induced thrombosis in aged individuals. Proc Natl Acad Sci USA 99: 890-895.
- Danø K, Andreasen PA, Grøndahl-Hansen J, Kristensen P, Nielsen LS, et al. (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44: 139-266.
- Landau BJ, Kwaan HC, Verrusio EN, Brem SS (1994) Elevated levels of urokinase-type plasminogen activator and plasminogen activator inhibitor tipe-1 in malignant human brain tumors. Fibrinolysis 8: 61.
- Farinati F, Hersszényi L, Plebani M, Carraro P, De Paoli M, et al. (1996) Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric. Carcinogenesis. Carcinogenesis 17: 2581-2587.
- McMahon B, Kwaan HC (2008) The plasminogen activator system and cancer. Pathophysiol Haemost Thromb 36: 184-194.
- Kwaan HC, Mazar AP, McMahon BJ (2013) The apparent uPA/PAI-1 paradox in cancer: More than meets the eye. Semin Thromb Haemost 39: 382-391.
- Zhang W, Ling D, Tan J, Zhang J, Li L (2013) Expression of urokinase plasminogen activator and plasminogen activator inhibitor type-1 in ovarian cancer and its clinical significance. Oncol Rep 29: 637-645.
- Cesari M, Pahor M, Incalzi RA (2010) Plasminogen activator inhibitor-1 (PAI-1): A key factor linking fibrinolysis and age-related subclinical and clinical conditions. Cardiovasc Ther 28: e72-e91.
- Pedersen H, Brunner N, Francis D, Osterlind K, Ronne E, et al. (1994) Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue. Cancer Res 54: 4671-4675.
- Bashar H, Urano T, Fukuta K, Pietraszek MH, Hata M, et al. (1994) Plasminogen activators and plasminogen activator inhiibitor 1 in urinary tract cancer. Urol Int 52: 4-8.
- Robert C, Bolon I, Gazzeri S, Veyrenc S, Brambilla C, et al. (1999) Expression of plasminogen activator inhibitor 1 and 2 in lung cancer and their role in tumor progression. Clin Cancer Res 5: 2094-2102.
- Zheng Q, Tang ZY, Xue Q, Shi DR, Song HY, et al. (2000) Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor. J Cancer Res Clin Oncol 126: 641-646.
- Duffy MJ (2002) Urokinase plasminogen activator and its inhibitor, PAI-1, as prognostic markers in breast cancer: From pilot to level 1 evidence studies. Clin Chem 48: 1194-1197.
- Kwaan HC, Wang J, Svoboda K, Declerck PJ (2000) Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis. Br J Cancer 82: 1702-1708.
- Sakakibara T, Hibi K, Koike M, Fujiwara M, Kodera Y, et al. (2006) Plasminogen activator inhibitor-1 as a potential marker for the malignancy of gastric cancer. Cancer Sci 97: 395-399.
- Binder BR, Mihaly J (2008) The plasminogen activator inhibitor “paradox” in cancer. Immunol Lett 118: 116-124.
- Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, et al. (2015) Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer. Cancer Biol Ther 16: 253-260.
- Li S, Wei X, Ela J, Tian X, Yuan SH, et al. (2018) Plasminogen activator inhibitor-1 in cancer research. Biomed Pharmacother 105: 83-94.
Citation: Lasierra-Cirujeda J, Aza-Pascual-Salcedo MJ, Aza-Pascual-Salcedo MM, Lasierra-Ibañez A, Lasala-Aza C (2019) Cancer: Stress and PAI-1. J Mol Genet Med 13:422.
Copyright: © 2019 Lasierra-Cirujeda J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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