Substance-P-Mediated Immunomodulation of Tumor Growth in a Murine Model

Manske, Jill M.; Hanson, Summer E.

doi:10.1159/000085652

Cited by 20 publications

(13 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Substance P has been shown to have proliferative and antiapoptotic effects via the mitogen-activated protein kinase cascade and nuclear factor-nB (18,19). Conversely, substance P inhibits melanoma formation in a murine model by a mechanism involving antitumor immunity (20). In the gastrointestinal tract, tachykinins regulate smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function (21).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer

Jin¹,

Olaru²,

Yang³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Our aim was to investigate whether and at what stage hypermethylation of the tachykinin-1 (TAC1) gene is associated with human esophageal neoplastic transformation. Experimental Design: TAC1 promoter hypermethylation was examined by real-time methylation-specific PCR in 258 human esophageal specimens and 126 plasma samples from patients or tissues at various stages of neoplastic evolution. Results: TAC1 hypermethylation in tissue samples showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P < 0.0001). Both frequencies and normalized methylation values ofTAC1 tissue methylation were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's esophagus, EAC, and ESCC than in normal esophagus (P < 0.01). The frequency of TAC1 hypermethylation increased dramatically and early during neoplastic progression, from 7.5% in normal esophagus to 55.6% in BE from patients with Barrett's metaplasia alone, 57.5% in dysplastic Barrett's esophagus, and 61.2% in EAC. There was a significant relationship between TAC1 hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Twelve (50%) of 24 ESCC exhibited TAC1 hypermethylation. Overall patient survival correlated significantly with TAC1 methylation status in ESCC patients (mean survival, 22 versus 110 months; P = 0.0102, log-rank test), but not in EAC patients. Both mean normalized methylation values and frequency of TAC1 hypermethylation in plasma samples were significantly higher in EAC patients than in control subjects. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2 ¶-deoxycytidine reduced TAC1 methylation and increased TAC1 mRNA expression. Conclusions:TAC1 promoter hypermethylation is a common event in both major histologic types of human esophageal carcinoma, occurs early, correlates with other progression risk factors in esophageal adenocarcinogenesis, and is a tissue biomarker of a poor prognosis in ESCC. Circulating methylated TAC1 promoter DNA also offers potential as a biomarker for the diagnosis of EAC.The tachykinin-1 (TAC1) gene has been mapped to chromosome 7q21-22 (1), a locus that frequently undergoes loss of heterozygosity in human cancers, including esophageal adenocarcinoma (EAC; refs. 2, 3). However, loss of heterozygosity is only one mechanism of gene inactivation; other common mechanisms include point mutation, homozygous deletion, and promoter methylation (4). It is now well established that promoter methylation correlates with transcriptional silencing in cancers (5), including esophageal squamous cell cancer (ESCC) and EAC (6, 7). Recently, data from our laboratory showed that the TAC1 promoter was methylated in 16 (47%) of 34 human colon cancers, and that the demethylating agent 5-aza-2 ¶-deoxycytidine (5-Aza-dC) reversed TAC1 promoter hypermethylation and restored TAC1 mRNA expression in colon cancer cell lines (8).

show abstract

Section: Discussionmentioning

confidence: 99%

Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer

Jin¹,

Olaru²,

Yang³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Moreover, several immune cells are capable of generating SP induced by stress, inflammation, or infection (569,570,596). For example, SP appears to be involved in keratinocyte/antigen-presenting cell interactions during chronic stress (569), T-cell regulation (607), natural killer cell activation (485), innate host defense (116), human immunodeficiency virus (HIV)-associated psoriasis (338,570), wound healing (189), murine hair follicle apoptosis (636), genital herpes infection (836), and immunosurveillance during experimentally induced tumor growth (murine melanoma) (509). SP may be also involved in inflammation and host responses of the CNS (511) as well as transmitting sensory signals (neurogenic inflammation, pain, pruritus) to the CNS (reviewed in Refs.…”

Section: Tachykinins and Neurokinin Receptorsmentioning

confidence: 99%

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

550

521

View full text Add to dashboard Cite

This review focuses on the role of the peripheral nervous system in cutaneous biology and disease. During the last few years, a modern concept of an interactive network between cutaneous nerves, the neuroendocrine axis, and the immune system has been established. We learned that neurocutaneous interactions influence a variety of physiological and pathophysiological functions, including cell growth, immunity, inflammation, pruritus, and wound healing. This interaction is mediated by primary afferent as well as autonomic nerves, which release neuromediators and activate specific receptors on many target cells in the skin. A dense network of sensory nerves releases neuropeptides, thereby modulating inflammation, cell growth, and the immune responses in the skin. Neurotrophic factors, in addition to regulating nerve growth, participate in many properties of skin function. The skin expresses a variety of neurohormone receptors coupled to heterotrimeric G proteins that are tightly involved in skin homeostasis and inflammation. This neurohormone-receptor interaction is modulated by endopeptidases, which are able to terminate neuropeptide-induced inflammatory or immune responses. Neuronal proteinase-activated receptors or transient receptor potential ion channels are recently described receptors that may have been important in regulating neurogenic inflammation, pain, and pruritus. Together, a close multidirectional interaction between neuromediators, high-affinity receptors, and regulatory proteases is critically involved to maintain tissue integrity and regulate inflammatory responses in the skin. A deeper understanding of cutaneous neuroimmunoendocrinology may help to develop new strategies for the treatment of several skin diseases.

show abstract

“…Studies indicate, however, that the effect of SP is dependent on the tumor model in which it is examined. While, in some models, SP has been found to stimulate tumor growth, other studies have documented the opposite effect (6)(7)(8)(9)(10)(11)(12)(13)(14)(28)(29)(30)(31). For example, it has been demonstrated that pre-treatment of mice with SP protects against melanoma growth by inducing anti-tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been demonstrated that pre-treatment of mice with SP protects against melanoma growth by inducing anti-tumor immunity. Additionally, silencing of the SP gene has been implicated in colon carcinogenesis (6,32). Flageole et al reported that SP increases the cytotoxic immune response to colorectal cancer cells (12).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, we observed that the depletion of SP from sensory nerve endings increased breast cancer metastases (4,5). Furthermore, treatment with SP decreased the growth of melanomas, small-cell lung cancer, colon cancer and prostate cancer (6)(7)(8)(9)(10)(11)(12)(13)(14). The role of SP during metastatic growth is therefore controversial, and requires further study.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Radiotherapy-induced decreases in substance P levels may potentiate melanoma growth

Erin¹

2009

Mol Med Rep

View full text Add to dashboard Cite

Abstract. Substance P, a member of the tachykinin family, is expressed in primary invasive malignant melanomas, metastatic melanomas, melanomas in situ, atypical naevi, and spindle and epithelioid cell naevi. The role of substance P in cancer development and progression is not clear. Radiotherapy, which is used extensively in the treatment of malignancies, alters substance P levels. It is, however, not known whether radiotherapy affects substance P levels in melanomas or in the tumor microenvironment. Given the fact that melanomas express substance P, possible radiation-induced changes in substance P content may underlie their radio-resistance. Hence, the aim of the present study was to determine the effects of radiotherapy on the growth of B16F10 melanomas as well as on the tumor and systemic expression of substance P. In vivo exposure of tumor-bearing C5BL/6 mice to ionizing radiation (45 Gy administered in three fractions) arrested tumor growth for three weeks and induced 3-fold increases in survival, as well as decreasing substance P levels in primary tumors and the surrounding skin. Although radiotherapy was applied locally (1 x 1 cm) at the mid-flank region of the animal, it also induced systemic changes in the levels of substance P. Specifically, radiotherapy decreased substance P levels in skin distant from the radiation field as well as in the lungs and adrenals. In order to understand the significance of this effect, B16F10 cells and cells made from metastatic lesions (B16LNAD cells) were treated with substance P. Substance P inhibited the growth of B16F10 and B16LNAD cells and further potentiated the inhibitory effects of radiotherapy. These findings demonstrate for the first time that substance P inhibits melanoma growth, and that radiotherapy-induced decreases in substance P levels may underlie the radio-resistance of melanomas.

show abstract

Substance-P-Mediated Immunomodulation of Tumor Growth in a Murine Model

Cited by 20 publications

References 97 publications

Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer

Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Radiotherapy-induced decreases in substance P levels may potentiate melanoma growth

Contact Info

Product

Resources

About