Early detection of biomarkers for circulating tumor cells in Bone marrow and Peripheral blood in a fast-progressing gastric cancer model.

Helicobacter pylori poses one of the greatest risks for development of gastric cancer. We previously established a crucial role for myeloid differentiation primary response 88 (MyD88) in the regulation of Helicobacter-induced gastric cancer. Mice deficient in Myd88 rapidly progressed to neoplasia when infected with H. felis, a close relative of H. pylori. For this study we examined circulating tumor cells (CTCs) by measuring expression of cytokeratins, epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) markers in in the bone marrow and peripheral blood of gastric cancer models we termed fast (Myd88-/-)- and slow (WT)-"progressors". We detected cytokeratins CK8/18 as early as 3 months post infection in the fast "progressors". In contrast, cytokeratins were not detected in slow "progressor" gastric cancer model even after 7 months post infection. Expression of 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. Expression of these EMT markers suggests manifestation of cancer metastasis in the early stages of disease development. Lgr5, CD44 and CD133 were the most prominent CSC markers detected. 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 will be important in stratifying patients for treatment before the onset of severe disease characteristics.