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

Norio Kitamura, Takeshi Iwamura, Shoji Taniguchi, Hideo Yamanari, Kikuo Kawano, Michael A Hollingsworth, Toshiaki Setoguchi

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)561-571
Number of pages11
JournalClinical and Experimental Metastasis
Volume18
Issue number7
DOIs
StatePublished - Dec 1 2000

Fingerprint

Pancreatic Neoplasms
Nude Mice
Cell Line
Matrix Metalloproteinases
Neoplasm Metastasis
Lung
Lung Volume Measurements
Matrix Metalloproteinase 1
Collagen Type IV
Pulmonary Veins
Collagenases
Collagen Type I
Extracellular Matrix
Tail
Veins
Collagen
Polymerase Chain Reaction

Keywords

  • Collagen-degradation
  • Human pancreatic cancer
  • In vivo selection
  • Invasion
  • Metastasis

ASJC Scopus subject areas

  • Cancer Research

Cite this

High collagenolytic activity in spontaneously highly metastatic variants derived from a human pancreatic cancer cell line (SUIT-2) in nude mice. / Kitamura, Norio; Iwamura, Takeshi; Taniguchi, Shoji; Yamanari, Hideo; Kawano, Kikuo; Hollingsworth, Michael A; Setoguchi, Toshiaki.

In: Clinical and Experimental Metastasis, Vol. 18, No. 7, 01.12.2000, p. 561-571.

Research output: Contribution to journalArticle

Kitamura, Norio ; Iwamura, Takeshi ; Taniguchi, Shoji ; Yamanari, Hideo ; Kawano, Kikuo ; Hollingsworth, Michael A ; Setoguchi, Toshiaki. / High collagenolytic activity in spontaneously highly metastatic variants derived from a human pancreatic cancer cell line (SUIT-2) in nude mice. In: Clinical and Experimental Metastasis. 2000 ; Vol. 18, No. 7. pp. 561-571.
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