Browsing by keyword "Helicobacter"

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    • How the study of Helicobacter infection can contribute to the understanding of carcinoma development
      Stoicov, Calin; Li, Hanchen; Cerny, Jan; Houghton, JeanMarie (2009-09-01)
      The inflammatory environment dramatically impacts the formation of cancer at many levels, acting on the stem cell to foster the initiation of cancer all the way through its contribution to metastatic disease. Using Helicobacter-induced gastric cancer as an example, it can be seen that, early on, chronic inflammation exhausts tissue stem cells, forcing the remaining stem cells to work overtime and calling in replacement cells from marrow sources. Marrow-derived stromal cells orchestrate growth and remodelling through secreted factors and cell-cell communication. Once cancer is present, the inflammatory environment is responsible for the continued growth signals to the cancer stem cells and to the stromal cells which become a vital part of the cancer niche as well as the pre-metastatic niche which will effectively lure cancer cells into peripheral organs for distant growth. This understanding of the inflammatory environment and its many effects on cancer throughout its natural history provides intervention targets directed at the unique aspects of cancer behaviour.

    • Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic, trafficking to gastric mucosal inflammation
      Stoicov, Calin; Li, Hanchen; Liu, Jian Hua; Houghton, JeanMarie (2013-09-01)
      BACKGROUND: Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis. AIM: To determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer. METHODS: SDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6 months or controls were given IV injections of CXCR4 knock-down MSC. Animals were followed for another 4 months. Homing of MSC in the stomach was quantified using RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using immunohistochemistry and fluorescent in situ hybridization. RESULTS: CXCR4 and SDF-1 are both upregulated in the settings of Helicobacter-induced chronic gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in acute gastric inflammation, but only partially in Helicobacter-induced gastric cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of Helicobacter infection. CONCLUSIONS: Our results show that MSC have a tumorigenic effect by promoting an accelerated form of gastric cancer in mice. The engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.