Publication: Cohort migration of carcinoma cells.Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets
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Date
1999
Authors
Nabeshima, K. ; Inoue, T. ; Shimao, Y. ; Kataoka, H. ; Koono, M.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Active migration of tumor cells is usually
assessed as single cell locomotion in vitro using Royden
chamber-type assays. In vivo, however, carcinoma cells,
malignant cells of epithelial origin, frequently invade the
surrounding tissue as coherent clusters or nests of cells.
We have called this type of movement "cohort
migration". In our work, the invasion front of colon
carcinomas consisted of compact tumor glands, partially
resolved glands or markedly resolved glands with
scattered tumor cell clusters or single cells lying ahead.
In the former two types, which constituted about a half
of all cases, cohort migration seems to be the
predominant mechanism, whereas both cohort migration
and single cell locomotion may be involved in the last
one. In this light, it is very advantageous to investigate
the mechanisms involved in the cohort migration.
In this review, we present a two-dimensional
motility assay as a cohort migration model, in which
human colorectal carcinoma cells move outwards from
the cell islands mainly as localized coherent sheets of
cells when stimulated with 12-0-tetradecanoylphorbol-
13-acetate (TPA) or hepatocyte growth factorlscatter
factor (HGFISF). Within the migrating cell sheets, wide
intercellular gaps occur at the lower portion of the cells
to allow the cells to extend leading lamellae forward
while close cell-cell contacts remain at the upper portion
of the cells. This localized modulation of cell-cell
adhesion at the lower portion of the cells is associated
with increased tyrosine phosphorylation of the Ecadherin-
catenin complex in TPA-induced cohort
migration and with reduced a-catenin complexed with
E-cadherin in HGFISF-induced cohort migration.
Furthermore, fibronectin deposited by migrating cells is
essential for their movement, and on the gelatin-coated
substrate even degradation and remodeling of the
substrate by matrix metalloproteinases are also needed.
Thus, in cohort migration it is likely that cells are
released from cell-cell adhesion only at the lower portion
Offprint requests to: Dr. Kazuki Nabeshima, Department of Pathology,
Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692,
Japan. e-mail: KAZNABES@post.miyazaki-med.ac.jp
Histology and
Histopathology
of the cells via modulation of E-cadherin-catenin-based
mechanism, and this change allows the cells to extend
leading lamellae onto the extracellular matrix substrate
remodeled by deposition of fibronectin and organized
digestion.
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