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

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

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.

Inclusion Criteria:

• · All the patients requiring an endoscopy within the framework of a colorectal cancer

  • All the patients requiring a low digestive endoscopy within the framework of the diagnosis or of the follow-up of a colorectal cancer, realized in the CHU of Nice.
  • Realization of a preliminary medical examination
  • Obligation for all the patients to be affiliated to the Social Security
  • Signature of the informed consent

Exclusion Criteria:

• • Pushed acute severe of the disease defined by the score of Truelove and Witss or the score of Lichtiger > 10 (cf appendix)

  • severe endoscopic Hurts returning the practice of dangerous additional biopsies
  • Disorders of the coagulation or the patient under anti-vitamin K, aspirin or clopidogrel.
  • Patient presenting an unchecked renal, respiratory, hepatic or cardiac insufficiency
  • Patient known positive HIV
  • vulnerable People: pregnant or breast-feeding women (a pregnancy test will be realized), minors, adults under guardianship or guardianships, deprived of freedom