High collagenolytic activity in spontaneously highly metastatic variants derived from a human pancreatic cancer cell line (SUIT-2) in nude mice |
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Authors: | Norio Kitamura Takeshi Iwamura Shoji Taniguchi Hideo Yamanari Kikuo Kawano Michael A Hollingsworth Toshiaki Setoguchi |
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Institution: | (1) Department of Surgery 1, Miyazaki Medical College, Miyazaki, Japan;(2) Eppley Institute for Research in Cancer and Allied disease, University of Nebraska Medical Center, Nebraska, USA |
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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.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | collagen-degradation human pancreatic cancer in vivo selection invasion metastasis |
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