A Screening System for Evaluating Cell Extension Formation, Collagen Compaction, and Degradation in Drug Discovery

Asuka Yuda, Christopher A. McCulloch

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

The generation of cell extensions is critical for matrix remodeling in tissue invasion by cancer cells, but current methods for identifying molecules that regulate cell extension formation and matrix remodeling are not well adapted for screening purposes. We applied a grid-supported, floating collagen gel system (~100 Pa stiffness) to examine cell extension formation, collagen compaction, and collagen degradation in a single assay. With the use of cultured diploid fibroblasts, a fibroblast cell line, and two cancer cell lines, we found that compared with attached collagen gels (~2800 Pa), the mean number and length of cell extensions were respectively greater in the floating gels. In assessing specific processes in cell extension formation, compared with controls, the number of cell extensions was reduced by latrunculin B, β1 integrin blockade, and a formin FH2 domain inhibitor. Screening of a kinase inhibitor library (480 compounds) with the floating gel assay showed that compared with vehicle-treated cells, there were large reductions of collagen compaction, pericellular collagen degradation, and number of cell extensions after treatment with SB431542, SIS3, Fasudil, GSK650394, and PKC-412. These data indicate that the grid-supported floating collagen gel model can be used to screen for inhibitors of cell extension formation and critical matrix remodeling events associated with cancer cell invasion.

元の言語英語
ページ(範囲)132-143
ページ数12
ジャーナルSLAS Discovery
23
発行部数2
DOI
出版物ステータス出版済み - 2 1 2018

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Drug Discovery
Screening
Compaction
Collagen
Degradation
Gels
Cells
4'-N-benzoylstaurosporine
Fibroblasts
Cell Count
Assays
Cell Line
Neoplasms
Integrins
Diploidy
Libraries
Phosphotransferases
Stiffness
Tissue
Molecules

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Molecular Medicine

これを引用

A Screening System for Evaluating Cell Extension Formation, Collagen Compaction, and Degradation in Drug Discovery. / Yuda, Asuka; McCulloch, Christopher A.

:: SLAS Discovery, 巻 23, 番号 2, 01.02.2018, p. 132-143.

研究成果: ジャーナルへの寄稿記事

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