The Gastrin-Releasing Peptide Receptor as a Marker of Dysplastic Alterations in Cervical Epithelial Cells

Abstract

Background: Cervical cancer is a leading cancer in women worldwide. The Papanicolaou test (Pap test) remains the main screening tool; however, it produces high rates of false-negative and false-positive results. Gastrin-releasing peptide is a growth factor that has been implicated in many cancers, and its main receptor, the gastrin-releasing peptide receptor (GRPR), is nearly always expressed in cervical dysplasias and invasive carcinomas. The aim of this study was to evaluate the diagnostic potential of GRPR immunocytochemistry in detecting cervical dysplasia and invasive cancer. Methods: Cervical smears were collected from 66 women in Brazil and subjected to GRPR immunocytochemistry and the Pap test. GRPR and p16 immunohistochemistry were performed in biopsies if abnormalities were detected. Results: GRPR immunostaining sensitivity in detecting cervical lesions was 87.5% and its specificity was 76.7%. GRPR immunostaining showed 80% accuracy in identifying atypical squamous cells of undetermined significance (ASCUS), with 88% sensitivity and 71% specificity. Conclusion: This is the first immunocytochemical evaluation of GRPR expression in cervical epithelial cells. This biomarker was strongly associated with cervical dysplasia and invasive cancers. GRPR immunosignaling showed high accuracy in detecting dysplasias in cells classified as ASCUS by Pap tests. Based on these results, immunocytochemistry for GRPR may be regarded as a valuable method for early detection of cervical intraepithelial neoplasia.

Gastrin‐releasing peptide receptor gene silencing inhibits the development of the epithelial–mesenchymal transition and formation of a calcium oxalate crystal in renal tubular epithelial cells in mice with kidney stones via the PI3K/Akt signaling pathway

“…Akt: protein kinase B; ANOVA: analysis of variance; FSP-1: fibroblast-specific protein-1; GRPR: gastrin-releasing peptide receptor; mRNA: messenger RNA; NC: negative control; PI3K: phosphatidylinositol 3-kinase; RT-qPCR: reversetranscription quantitative polymerase chain reaction; SD: standard deviation; TEC: tubular epithelial cell the activation of the PI3K/Akt signaling pathway, thus suppressing the development of the EMT and formation of the calcium oxalate crystal in renal TECs.During our study, the results showed that GRPR via inhibiting the PI3K/Akt signaling pathway downregulates the development of EMT.GRPR belongs to the G-protein receptor superfamily and leads to cell proliferation and growth by the activation of several signal transduction pathways(Flores et al, 2010). The overexpression of GRPR is observed in many human malignant tumors, acting as a molecular target in the anticancer therapy(Cornelio, Meurer, Schwartsmann, & Roesler, 2012). The main feature of EMT is the transformation of tightly attached and cuboidal epithelial cells into unanchored and extended mesenchymal type cells, which exhibit actin reorganization, loss of epithelial cell adhesion, and increased cell migration and invasion in renal fibrosis(McMorrow, Gaffney, Slattery, Campbell, & Ryan, 2005).…”

“…GRPR belongs to the G-protein receptor superfamily and leads to cell proliferation and growth by the activation of several signal transduction pathways (Flores et al, 2010). The overexpression of GRPR is observed in many human malignant tumors, acting as a molecular target in the anticancer therapy (Cornelio, Meurer, Schwartsmann, & Roesler, 2012). The main feature of EMT is the transformation of tightly attached and cuboidal epithelial cells into unanchored and extended mesenchymal type cells, which exhibit actin reorganization, loss of epithelial cell adhesion, and increased cell migration and invasion in renal fibrosis (McMorrow, Gaffney, Slattery, Campbell, & Ryan, 2005).…”

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

“…GRPR activation has been shown to stimulate cancer cell proliferation, whereas GRPR antagonists to reduce tumor growth in a range of experimental cancer models (1,2). In gynecologic cancers, GRPR is likely to be highly expressed in breast, ovarian and cervical tumors, as well as in breast cancer cell lines, whereas its expression is low or absent in non-neoplastic tissue and healthy cells (1,(3)(4)(5)(6)(7)(8). The pharmacological blockade of GRPR by synthetic peptides acting as selective antagonists (RC-3940-II, RC-3095) has been shown to reduce human breast and ovarian tumor growth xenografted into nude mice (9)(10)(11).…”

Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer

“…Molecularly targeted radiopharmaceuticals are being tested in a variety of oncologic settings ( 14 , 15 ). Because GRPR occurs and stimulates cell proliferation in uterine cervix cancer ( 7 – 9 ), radiopharmaceutical peptide–receptor cohesion might have a therapeutic value by bringing a cell-killing radionuclide directly to cancer cells. The 212 Pb-DOTAM-GRPR1 radiopharmaceutical is an α-particle-emitting radionuclide 212 Pb, a metal chelator DOTAM, and a GRPR-targeted antagonist that is currently being studied in the metastatic uterine cervix cancer setting (NCT05283330) as well as in a variety of other cancer types.…”