Neuropeptide Substance P Enhances Inflammation-Mediated Tumor Signaling Pathways and Migration and Proliferation of Head
- PDF / 1,751,765 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 162 Views
ORIGINAL ARTICLE
Neuropeptide Substance P Enhances Inflammation-Mediated Tumor Signaling Pathways and Migration and Proliferation of Head and Neck Cancers Sumeet Singh 1 & Subhashree Kumaravel 1 & Saurabh Dhole 1 & Sukanya Roy 1 & Vani Pavan 1 & Sanjukta Chakraborty 1 Received: 22 April 2020 / Accepted: 25 August 2020 # Indian Association of Surgical Oncology 2020
Abstract Head and neck cancers (HNC) are extremely aggressive, highly recurrent, and the sixth most common cancer worldwide. Neuropeptide substance P, along with its primary receptor, neurokinin-1 (NK-1R), is overexpressed in HNC and is a central player in inflammation and growth and metastasis of several cancers. However, the precise SP-mediated signaling that promotes HNC progression remains ill defined. Using a panel of HNC lines, in this study, we investigated the effects of SP on proliferation and migration of HNC. Tumor cells were also treated with SP and alterations in inflammatory cytokines and chemokines, and their cognate receptors were analyzed by real-time PCR. Furthermore, we investigated the role of SP in inducing epithelialmesenchymal transition (EMT), and matrix metalloproteases that promote tumor invasion. Our results showed that SP significantly increased tumor cell proliferation and migration and induced the expression of several genes that promote tumor growth, invasion, and metastasis which was suppressed by a specific NK1R antagonist L-703606. SP also activated NFκB that was suppressed on inhibiting NK1R. Collectively, our data shows that SP-NK1R-mediated inflammatory signaling comprises an important signaling axis in promoting HNC and may prove to be effective clinical target against HNC cells that are resistant to traditional therapy. Keywords Neuropeptide . Inflammation . Cytokines . Head neck cancer . Tumor progression
Introduction Head and neck cancers (HNC) annually contribute to approximately 650,000 or 6% of new cancers worldwide, as well as over 300,000 deaths [1]. These cancers comprise a multitude of malignancies that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol and are one of the most aggressive among solid tumors [2, 3]. HNC is known to be frequently recurrent and primarily metastatic, with the percentage of clinical metastasis ranging from 4 to 26%. Patients that have developed distant metastasis with HNC have a poor prognosis with an overall 5year survival rate and often elude traditional therapeutic regimens [4]. * Sanjukta Chakraborty [email protected] 1
Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Medical Research and Education Building, 8447 Riverside Parkway, Bryan, TX 77807, USA
Several neuropeptides have been associated with enhanced tumorigenesis of HNC cells. One such molecule that mediates inflammatory signaling cascades and is significantly involved in promotion of cancer metastasis is substance P (SP), which is central to the pathogenesis of various solid and hematological cancers [5]. SP is a mamm
Data Loading...
