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Decoding of the Expression of Tumor Suppressor P2RX7 in Inflammatory and Malignant Colonic Mucosa

NCT02293811 · Status: TERMINATED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 50

Last updated 2024-03-18

No results posted yet for this study

Summary

The inflammatory tumor micro-environment is a consequence and a driver of tumorogenesis. On one hand it promotes antitumor immune responses and on the other hand it favors development and progression of cancerous lesions.

Factors regulating the complex interplay between epithelial and immune cells are still poorly characterized. Extracellular ATP (eATP) acting on the purinergic P2X7 receptors (P2RX7) has recently emerged as a key signaling pathway in the immune response.

Recent data have revealed the crucial role of P2RX7-NLRP3-Caspase-1 for priming dendritic cells (DC) within the tumor microenvironment upon treatment with certain types of chemotherapy drugs. Despite this important discovery, no previous study has so far investigated the global in vivo effect of P2RX7 modulation in inflammation-induced carcinogenesis of mucosal tissues.

Our consortium, endowed by a long standing experience in the field of mucosal immunology, inflammation and signaling, already demonstrated that the P2RX7 is differentially expressed in the mucosa of patients with active and quiescent inflammatory bowel disease (IBD), where eATP is present at very high concentration, and that P2RX7 controls an amplification loop of the inflammatory response (Cesaro et al., 2010). Furthermore, we uncovered that P2RX7 controls homeostasis, survival and function of regulatory T cells (Hubert et al., 2010). In addition, our recent demonstration that P2RX7 deficiency lowered mucosal inflammation but unexpectedly enhanced tumor formation in vivo warrants additional efforts to explore the molecular and cellular mechanisms accounting for this effect and suggest that enhancing P2RX7 function may have an anti-tumor therapeutic effect.

These observations emphasize the tumor suppressor role of P2X7 receptor, warrant further investigation to better understand the molecular mechanisms responsible for this anti-tumor effect and suggest that enhancing the function of P2X7R could have a therapeutic effect significant antitumor.

Our main objectives is to explore the role of P2RX7 in healthy, inflammatory and cancerous colonic mucosa. For this we will map the expression of the protein P2RX7 and realize genotype of P2RX7 forms in inflammatory diseases and cancer of the colon.

Conditions

  • Crohn Disease-Associated Colorectal Adenocarcinoma

Interventions

OTHER

Analysis

An additional blood sample (10ml) will be taken on the day of hospitalization to achieve the genomic studies in search of mutations in constitutional DNA of circulating lymphocytes and acquired mutations of DNA circulating. We will use the technique of tissue-microarray to analyze the expression level of P2RX7 both in epithelial cells than in stromal cells inflammatory. Genotyping will be conducted partly on colonic biopsies and also on blood samples (to demonstrate the feasibility of this technique much less debilitating).

Sponsors & Collaborators

  • Centre Hospitalier Universitaire de Nice

    lead OTHER

Principal Investigators

  • HEBUTERNE Xavier, PhD · CHU de Nice, Hôpital Archet, Gastroentérologie

Study Design

Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-02-09
Primary Completion
2015-10-15
Completion
2015-12-15

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02293811 on ClinicalTrials.gov