Helicobacter pylori, gastrin and cyclooxygenases tn gastric cancer

Background: Tumors arising in the stomach have worldwide distribution and t he infection with Helicobacter pq (ori (HP) has been implicated in causatio n of this disease. The HP discovery, which is considered as the greatest ad vance of gastroenterology at the dawn of 3(rd) millennium, is accompanied b y hypergastrinemia, which seems to play a key role in gastric cancerogenesi s but no study was undertaken to assess the relationship between the HP inf ection and coexpression of gastrin and cyclooxygenases (COX), the rate limi ting enzymes in the eicosanoids production. Aims: Since gastrin is recogniz ed as a effective gastric mitogen, it could be capable to induce COX-2, a p otent tumor growth promoting and angiogenic Factor, we decided 1) to compar e the seroprevalence of HP and its cytotoxic protein, CagA, in gastric canc er patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCKB-R) in gastric cance r, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX- 1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication. Material and Methods. The trial material included 20 patients with gastric cancers and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCKB-R, COX-1 and COX-2 was examined u sing RT-PCR with GAPDH as a reference and employing Western blot for COX-2 expression, while gastrin was measured by RIA. Results. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric cancers than in controls. Both gastrin and CCKB-R mRNA were detected by RT -PCR in the cancer tissue and similarly COX-2 mRNA and protein were found i n most of cancers and in the HP infected antral mucosa but not in HP eradic ated patients in whom only cancer tissue but not gastric mucosa expressed C OX-2. The gastric cancer tissue contained 20 times more of immunoreactive g astrin than the HP infected antral gastric mucosa and following HP eradicat ion the gastrin content in the tumor and antrum showed a marked and signifi cant reduction. No significant change in CCKB-R expression was noticed befo re and after HP eradication in the tumor and the corpus mucosa. Conclusions: 1). Gastric carcinoma coexpresses gastrin, its receptors (CCKB -R), and COX-2; 2) HP infection may contribute to gastric cancerogenesis vi a gastrin and COX-2 that may account for the stimulation of tumor growth, a ngiogenesis, and reduction in apoptosis 3) HP positive patients developing gastric cancer should be considered for HP eradication to reduce the HP pro voked hypergastrinemia and COX-2 overexpression in the tumor tissue.