Early detection of tumor cells in bone marrow and peripheral blood in a fast-progressing gastric cancer model

Helicobacter pylori (H. pylori) infection is a major risk factor for the development of gastric cancer. The authors previously demonstrated that in mice deficient in myeloid differentiation primary response 88 (Myd88(−/−)), infection with Helicobacter felis (H. felis) a close relative of H. pylori, subsequently rapidly progressed to neoplasia. The present study examined circulating tumor cells (CTCs) by measuring the expression of cytokeratins, epithelial-to-mesenchymal transition (EMT)-related markers and cancer stem cell (CSC) markers in bone marrow and peripheral blood from Myd88(−/−) and wild-type (WT) mice. Cytokeratins CK8/18 were detected as early as 4 months post-infection in Myd88(−/−) mice. By contrast, cytokeratins were not detected in WT mice even after 7 months post-infection. The expression of Mucin-1 (MUC1) was observed in both bone marrow and peripheral blood at different time points, suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. The expression of these EMT-related markers suggests the manifestation of cancer metastasis in the early stages of disease development. LGR5, CD44 and CD133 were the most prominent CSC markers detected. The detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information may prove to be of significance in stratifying patients for treatment prior to the onset of severe disease-related characteristics.