Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours

Moles, M.A. González; Mosqueda‐Taylor, Adalberto; Esteban, Francisco; Gil-Montoya, José Antonio; Díaz-Franco, Marco Antonio; Delgado, M. Dolores; Muñoz, Miguel

doi:10.1016/j.oraloncology.2008.02.010

Cited by 41 publications

(30 citation statements)

References 38 publications

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“…SP, an undecapeptide of the tachykinin peptide family, regulates multiple biological functions by binding to the NK-1 receptor (NK-1R), including cardiovascular and respiratory mechanisms, sensory perception, and response to stress, among others (7)(8)(9)(10). However, one of its most important functions is related to its action as a potent mitogen on some precancerous epithelial lesions and some human cancer cell lines, e.g., glioma, retinoblastoma, neuroblastoma, melanoma, and laryngeal carcinoma as previously reported by our group (6,(11)(12)(13)(14)(15)(16)(17). These observations suggest that SP may play a role in cancer development by acting as a promoter of cell growth.…”

Section: Introductionmentioning

confidence: 88%

Substance P and NK-1R expression in oral precancerous epithelium

González‐Moles

Brener²,

Ruiz‐Ávila³

et al. 2009

Oncol Rep

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Abstract. The objectives of this study were to investigate the presence and distribution of substance P and neurokinin 1 receptor in oral premalignant epithelium and their relation with the presence of dysplasia, and to analyze whether the expression of substance P can be considered an early oncogenic event in oral carcinogenesis. Substance P and neurokinin 1 receptor expression was immunohistochemically studied in 83 oral carcinomas and adjacent nontumor epithelia. The presence and degree of epithelial dysplasia was assessed according to WHO criteria. The nuclear, cytoplasmic, and membrane expression of substance P and the cytoplasmic and membrane expression of neurokinin 1 receptor were assessed in tumor and adjacent non-tumor epithelium. Nuclear and cytoplasmic expression of substance P in non-tumor epithelium was significantly associated with the presence of epithelial dysplasia (p<0.001) and carcinoma in situ (p=0.021). Nuclear, cytoplasmic, and membrane expressions of substance P in non-tumor epithelium were significantly (p<0.001) associated with its expression in the corresponding tumor. These findings suggest that substance P plays a role in early oral carcinogenesis by promoting the proliferation and growth of premalignant fields. IntroductionThe development of oral carcinoma is a multistep process involving multiple oncogenic alterations (1). Some of these are considered early oncogenic events, including changes in chromosomal regions 3p, 9p, and 17p (2,3). Although tumor suppressor genes and putative oncogenes in these regions have yet to be identified (4), these chromosomal areas are known to be carriers of important cell-cycle and apoptosis-regulating genes. Thus, CDKN2A locus, which encodes for p16 protein, is located in chromosome 9p21, and p53 gene is in chromosome 17p13 (5). These early oncogenic events have been demonstrated in precancerous fields (4) and endow cells with an increased proliferation rate that affords them a growth advantage over epithelial cells of the adjacent healthy oral mucosa. This phenomenon considerably increases the number of target cells in which new oncogenic events can take place, which would ultimately lead to the development of one or more invasive carcinomas (4).There has been increasing interest over the past few years in the role of substance P (SP) in the development and progression of certain types of tumor (6). SP, an undecapeptide of the tachykinin peptide family, regulates multiple biological functions by binding to the NK-1 receptor (NK-1R), including cardiovascular and respiratory mechanisms, sensory perception, and response to stress, among others (7-10). However, one of its most important functions is related to its action as a potent mitogen on some precancerous epithelial lesions and some human cancer cell lines, e.g., glioma, retinoblastoma, neuroblastoma, melanoma, and laryngeal carcinoma as previously reported by our group (6,(11)(12)(13)(14)(15)(16)(17). These observations suggest that SP may play a role in cancer development by acting as a promot...

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Section: Introductionmentioning

confidence: 88%

Substance P and NK-1R expression in oral precancerous epithelium

González‐Moles

Brener²,

Ruiz‐Ávila³

et al. 2009

Oncol Rep

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“…It known that SP is expressed in keratocystic odontogenic tumors, oral squamous cell carcinoma, larynx carcinoma, blast cells, melanoma, glioma, retinoblastoma, neuroblastoma and lung cancer (González-Moles et al 2008;Brener et al 2009;Esteban et al 2009;. SP has been located in the cytoplasm and in the nucleus of tumor cells (González-Moles et al 2008;Brener et al 2009;Esteban et al 2009;Muñoz et al 2012).…”

Section: Cancermentioning

confidence: 99%

“…SP has been located in the cytoplasm and in the nucleus of tumor cells (González-Moles et al 2008;Brener et al 2009;Esteban et al 2009;Muñoz et al 2012). Moreover, the PPT1 gene is expressed more in breast cancer than in epithelial breast cells (Singh et al 2000).…”

Section: Cancermentioning

confidence: 99%

“…Moreover, the PPT1 gene is expressed more in breast cancer than in epithelial breast cells (Singh et al 2000). NK-1 receptors have also been demonstrated in human cancer cell lines and/or in primary tumors [e.g., glioma, astrocytoma, retinoblastoma, ganglioneuroblastoma, leukemia, neuroblastoma, carcinomas (pancreatic, larynx, gastric, colon, medullary thyroid, breast, oral)] (Friess et al 2003;González-Moles et al 2008;Brener et al 2009;Esteban et al 2009;Muñoz et al 2007;. It is also known that tumor cells overexpress NK-1 receptors, in comparison with non-tumor cells (Singh et al 2000;Friess et al 2003;Muñoz et al 2012) (Fig.…”

Section: Cancermentioning

confidence: 99%

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Involvement of substance P and the NK-1 receptor in human pathology

2014

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The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also present in cells not belonging to the nervous system (immune cells, liver, lung, placenta, etc.). SP is located in all body fluids, such as blood, cerebrospinal fluid, breast milk, etc. i.e. it is ubiquitous in human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration. SP has been also implicated in pain, inflammation, hepatitis, hepatotoxicity, cholestasis, pruritus, myocarditis, bronchiolitis, abortus, bacteria and viral infection (e.g., HIV infection) and it plays an important role in cancer (e.g., tumor cell proliferation, antiapoptotic effects in tumor cells, angiogenesis, migration of tumor cells for invasion, infiltration and metastasis). This means that the SP/NK-1 receptor system is involved in the molecular bases of many human pathologies. Thus, knowledge of this system is the key for a better understanding and hence a better management of many human diseases. In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.

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“…57 Antagonists for the preferential substance P receptor NK-1 are in clinical use for the treatment of anxiety and depressive disorders. 58 There is an increasing body of reports concerning NK-1 receptor involvement in cancer cell proliferation, [59][60][61] as well as migration and metastasis formation. 49,62,63 Therefore, substance P might complement the function of norepinephrine and the inhibition of the NK-1 receptor might serve as a new target in cancer therapy in some types of cancer in analogy to β-blockers.…”

confidence: 99%