Tumor hypoxia correlates with metastatic tumor growth of pancreatic cancer in an orthotopic murine model

The Journal of Surgical Research
Peter BüchlerOscar J Hines

Abstract

The role of tumor hypoxia has become a major focus in cancer research since it influences both local and systemic tumor growth. Oxygen measurements taken in human pancreatic cancer have shown extremely low oxygen tension. The aim of this study was to develop an orthotopic model for pancreatic cancer that mimics the specific tumor microenvironment and to evaluate the role of tumor oxygenation in local tumor growth and systemic dissemination in this model. We used two established human pancreatic cancer cell lines for xenobiotic tumor induction. After subcutaneous tumor formation one small tumor piece was transplanted into the pancreatic parenchyma of mice of the different study groups. Upon orthotopic tumor induction tumor oxygenation was measured with the Eppendorf histograph. Histological evaluation was performed with pimonidazole, an in vivo marker of hypoxia. The tumor take rate was 100% in this model. Metastatic tumor dissemination occurred within the abdominal cavity, and distant metastasis were observed in the lung parenchyma. Oxygen measurements taken in various abdominal organs and xenograft tumor showed a high variation between different organs and xenografted tumors. Tumor oxygenation correlated well with the metastat...Continue Reading

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