Reduced CD73 expression and its association with altered purine nucleotide metabolism in colorectal cancer cells robustly causing liver metastases

Abstract

Liver metastases of colorectal cancers significantly affect the prognoses of patients. To further understand the biological aspects of the metastatic phenotypes, we established the highly liver-metastatic human colorectal cancer cell subline SW48LM2. The subline was established through the serial intrasplenic transfer of cells derived from poor but visible hepatic tumor foci formed by parental SW48 cells and transferred to NOD/SCID/IL-2Rγcnull mice. The growth, both under monolayer culture conditions and during the formation of subcutaneous tumors, was similar between the two cell lines, although there were morphological differences in the in vitro spheroid formation. Of 41 molecules reportedly associated positively or negatively with tumor progression, four were overexpressed and four were underexpressed in SW48LM2 cells. Notably, this liver-metastatic cell subline exhibited a strongly reduced expression of the ecto-5'-nucleotidase CD73 as well as an altered metabolism of purine nucleotides. Previous studies showed a positive correlation between CD73 expression and metastatic cancer phenotypes. A reduced CD73 expression in tumor cells, however, may contribute to obtaining insight into the mechanisms of liver metastases.