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

Abstract

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-2Rγc null 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.

Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon‐26 tumor‐bearing mouse model in vivo

“…Liver metastases are frequently inoperable and significantly affect the prognoses of patients with cancer . Therefore, to determine the effect of MSE on liver metastasis, colon‐26 tumor cells were implanted into the spleens of female BALB/c mice to produce liver metastases (tumor nodules).…”

Characterization and Propagation of Tumor Initiating Cells Derived from Colorectal Liver Metastases: Trials, Tribulations and a Cautionary Note

“…Currently, in most articles reporting propagation of colorectal metastases in the liver, intrasplenic/orthotopic injection of a variety of established human colorectal cancer cell lines (including HCT116, HT29, SW480 and SW48) has been used [ 44 – 46 ]. Other strategies rely upon extrapolation of invasive characteristics of established cell lines in in vitro systems in order to stratify colorectal cancer cells as ‘metastatic’, rather than deriving them experimentally from patients’ metastases [ 47 , 48 ].…”

Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma

“…The BxPC-3 human PDC cell line was purchased from the American Type Culture Collection (Manassas, VA, USA). A highly liver-metastatic cancer cell subline, LM-BxPC-3, was established via the intrasplenic transfer of cells derived from poorly developed but visible hepatic tumor foci formed following transplantation of the parental BxPC-3 cells and transfer to NOD/Shi-scid/IL-2Rγ null (NOG) mice at the Central Institute for Experimental Animals (CIEA; Kanagawa, Japan) ( 11 , 15 , 16 ). The cells were cultivated in RPMI-1640 medium (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany) supplemented with 10% fetal bovine serum (BioWest, Nuaillé, France) in a humidified (37°C, 5% CO 2 ) incubator, and passaged on reaching 80% confluence.…”

“…To create subcutaneous models, 1×10 4 BxPC-3 tumor cells suspended in 0.1 ml serum-free RPMI-1640 medium (Sigma-Aldrich; Merck KGaA) were injected into the subcutis of the mice. The experimental liver metastasis models were generated via intrasplenic injection of 1×10 4 LM-BxPC-3 cells in 0.1 ml serum-free medium, followed by splenectomy after 1 min, as previously described ( 11 , 15 , 16 ). The mice were sacrificed under anesthesia and necropsied 6–8 weeks after inoculation, according to the standard protocols of the CIEA.…”