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Abstract

Cell lines with high metastatic capacity to the lung were established by sequential passage of a human pancreatic cancer cell line (SUIT-2) through the lung of a nude mouse, via the lateral tail vein and from a subcutaneous inoculum. Cells of the parental SUIT-2 and sublines S2-VPx (x-cycle selection from SUIT-2 cells, by Vein-Pulmonary metastasis-culture) and S2-CPx (x-cycle selection, by Cutis-Pulmonary metastasis-culture) were injected intravenously or subcutaneously into nude mice to produce experimental or spontaneous lung metastasis. The S2-VP10 cell line produced pulmonary metastases in 100% of the nude mice, when injected intravenously. It failed, however, to produce more lung colonies than its parent cell line, when injected subcutaneously. The S2-CP8 cell line produced extensive pulmonary metastases in 100% of the nude mice, when injected either intravenously or subcutaneously. This study indicates that the nude mouse provided a good model for in vivo selection of metastatic cells from SUIT-2 cells both experimentally and spontaneously, and that the SUIT-2, S2-VPx, and S2-CPx cell lines will be valuable in the study of human cancer metastasis. We previously reported high levels of ezrin expression in the S2-VP10 and S2-CP8 cell lines. Here we show that these cell lines exhibit a greater capacity to invade or attach to various extracellular matrix components than the parent SUIT-2 cells. The S2-CP8 cell lines also exhibit greater level of type-I and type-IV collagen-degrading activity than the parent SUIT-2 cell line and the S2-VP10 cell line, which shows similar collagen-degrading activity to the parent SUIT-2 cells. In RT-PCR studies, SUIT-2, S2-CP8 and S2-VP10 cell lines constitutively expressed many matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP7, MMP-9, MMP-10 and MMP-14). These results suggest that some parameters that enhance adhesion and invasion are important to both experimental and spontaneous metastasis and the collagen degrading enzymes are predicted to play a key-role during spontaneous metastasis.

Establishment and Characterization of a Novel Human Pancreatic Cancer Cell Line (SUIT-4) Metastasizing to Lymph Nodes and Lungs in Nude Mice

“…We previously reported that type-1 collagenolytic activity (mostly by MMP-1) is positively correlated with spontaneous metastatic potential [8, 23]. Actually, SUIT-4 expressed MMP-1, though it did not express MMP-2 and MMP-9.…”

Suppressive Effect of Shichimotsu-koka-to (Kampo Medicine) on Pulmonary Metastasis of B16 Melanoma Cells.

“…Reactive oxygen species (ROS), which are generated by tumor or endothelial cells, are known to play important roles in tumor invasion and metastasis. Expression of P-selectin increases with the exposure of pancreatic tumor cells to ROS, 29) and expression of VLA-4 on B16 melanoma cells also increases Male C57BL/6 mice received SKT, which was dissolved in daily intake of drinking water at the indicated doses, for 6 weeks. Thioglycollate-eliciting macrophages and B16 melanoma-conditioned medium were prepared as described in Materials and Methods.…”

Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer

“…MiaPaCa-2 was derived from a primary PDAC and Suit-2 was derived from a metastatic PDAC from a different patient (18). Cell lines were authenticated using STR profile analysis (ATCC) and tested for contamination (LookOut qPCR-ProbeKit, Sigma) within 6 months of the last experiment.…”