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

Abstract

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...

Role of neurotransmitter Substance P in progression of oral squamous cell carcinoma

“…In another study, an increase in SP and its receptor, Neurokinin 1 (NK-1R) expression was observed in precancerous oral epithelium and adjacent non-tumor epithelium, and it was suggested that SP plays a role in early carcinogenesis by promoting the proliferation and growth of premalignant fields [27], but in our study we have observed increased expression in an advanced stage of cancer rather than in an early stage. Very less positivity was observed in an early stage of cancer in the current study.…”

Prognostic significance of Substance P/ Neurokinin 1 receptor and its association with hormonal receptors in breast carcinoma

“…Overexpression of SP and NK-1R was also observed in pre-cancerous epithelium and it was proposed that it has contribution towards early carcinogenesis by increasing cell growth, cell division [41], however, in current study, this trend was found in later stage of In a recent case report published by Munoz M, a patient with chronic obstructive pulmonary disease and non-small cell lung carcinoma was treated with radiotherapy plus NK-1R antoagonist, aprepitant, for 45 days. The patient remained in good health, with no side effects and the tumor volume also decreased [42].…”

Neuroendocrine Factors and Head and Neck Squamous Cell Carcinoma: An Affair to Remember

“…In another study, it was evaluated by immunohistochemistry the expression of SP and NK-1R in oral SCC and adjacent nontumoral epithelium. It was investigated also the relationship of this expression with the presence of dysplasia [ 90 ]. Nuclear and cytoplasmic expression of SP in the nontumoral epithelium was significantly associated with the presence of epithelial dysplasia and carcinoma in situ.…”