High collagenolytic activity in spontaneously highly metastatic variants derived from a human pancreatic cancer cell line (SUIT-2) in nude mice

Cell lines with high metastatic capacity to the lung were established by se quential passage of a human pancreatic cancer cell line (SUIT-2) through th e lung of a nude mouse, via the lateral tail vein and from a subcutaneous i noculum. Cells of the parental SUIT-2 and sublines S2-VPx (x-cycle selectio n from SUIT-2 cells, by Vein-Pulmonary metastasis-culture) and S2-CPx (x-cy cle selection, by Cutis-Pulmonary metastasis-culture) were injected intrave nously or subcutaneously into nude mice to produce experimental or spontane ous 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 subcut aneously. The S2-CP8 cell line produced extensive pulmonary metastases in 1 00% 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 sp ontaneously, and that the SUIT-2, S2-VPx, and S2-CPx cell lines will be val uable 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 sh ow that these cell lines exhibit a greater capacity to invade or attach to various extracellular matrix components than the parent SUIT-2 cells. The S 2-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 li ne, which shows similar collagen-degrading activity to the parent SUIT-2 ce lls. In RT-PCR studies, SUIT-2, S2-CP8 and S2-VP10 cell lines constitutivel y 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 enha nce adhesion and invasion are important to both experimental and spontaneou s metastasis and the collagen degrading enzymes are predicted to play a key -role during spontaneous metastasis.