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Morphophenotype of floating colonies derived from a single cancer cell has a critical impact on tumor‐forming activity
Author(s) -
Ishii Genichiro,
Hashimoto Hiroko,
Atsumi Naho,
Hoshino Ayuko,
Ochiai Atsushi
Publication year - 2013
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12018
Subject(s) - biology , adenocarcinoma , cancer cell , cell , cell culture , cancer , epithelial–mesenchymal transition , pathology , microbiology and biotechnology , metastasis , medicine , genetics
The anchorage‐independent colony growth of cancer cells is reportedly correlated with the tumor‐forming activity; however, the correlation between the morphophenotype of each colony and the tumor‐forming activity has not been clarified. To assess this problem, we cultured single A 549 cells (human lung adenocarcinoma cell line) in growth medium in individual wells (n = 426) for 14 days under anchorage‐independent conditions and analyzed the resulting growth characteristics. The single A 549 cells formed various sizes of floating colonies. The proportion of large colonies (>400 μm) was 3.8% and this proportion increased dramatically with the exogenous addition of EGF (21.6%) or HGF (27.6%). Morphologically, the floating colonies could be divided into: (ii) Type A, spheroid colony; and (ii) Type B , dispersed villous colony. The Type B colonies expressed significantly higher levels of epithelial‐mesenchymal transition ( EMT )‐related m RNA s ( S nail 1, ZEB 1, and ZEB 2) than the Type A colonies. Furthermore, the subcutaneous injection of a single cell‐derived colony with a large size and a Type B morphology resulted in more efficient tumor formation. The present results indicated that the morphophenotypes of floating colonies derived from single cancer cells have a critical impact on tumor‐forming activity.