Open AccessIrradiated fibroblast‐induced bystander effects on invasive growth of squamous cell carcinoma under cancer–stromal cell interaction
Author(s) -
Kamochi Noriyuki,
Nakashima Masahiro,
Aoki Shigehisa,
Uchihashi Kazuyoshi,
Sugihara Hajime,
Toda Shuji,
Kudo Sho
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00978.x
Subject(s) - fibroblast , microbiology and biotechnology , stromal cell , cell growth , apoptosis , cancer research , chemistry , cell culture , biology , biochemistry , genetics
The irradiated fibroblast‐induced response of non‐irradiated neighboring cells is called ‘radiation‐induced bystander effect’, but it is unclear in non‐irradiated human squamous cell carcinoma (SCC) cells. The present study shows that irradiated fibroblasts promoted the invasive growth of T3M‐1 SCC cells, but not their apoptosis, more greatly than non‐irradiated fibroblasts, using collagen gel invasion assay, immunohistochemistry and Western blot. The number of irradiated fibroblasts decreased to about 30% of that of non‐irradiated fibroblasts, but irradiated fibroblasts increased the growth marker ki‐67 display of SCC cells more greatly than non‐irradiated fibroblasts. Irradiated fibroblasts did not affect the apoptosis marker ss‐DNA expression of SCC cells. Irradiated fibroblasts enhanced the display of the following growth‐, invasion‐ and motility‐related molecules in SCC cells more greatly than non‐irradiated fibroblasts: c‐Met, Ras, mitogen‐activated protein kinase (MAPK) cascade (Raf‐1, MEK‐1 and ERK‐1/2), matrix metalloproteinase‐1 and ‐9, laminin 5 and filamin A. Irradiated fibroblasts, but not non‐irradiated ones, formed irradiation‐induced foci (IRIF) of the genomic instability marker p53‐binding protein 1 (53BP1) and expressed transforming growth factor‐β1 (TGF‐ β1). Irradiated fibroblasts in turn enabled SCC cells to enhance 53BP1 IRIF formation more extensively than non‐irradiated fibroblasts. Finally, effects of irradiated fibroblasts on growth and apoptosis of another HEp‐2 SCC cell type were similar to those of T3M‐1. These results suggest that irradiated fibroblasts promotes invasion and growth of SCC cells by enhancement of invasive growth‐related molecules above through TGF‐ β1‐mediated bystander mechanism, in which irradiated fibroblast‐induced genomic instability of SCC cells may be involved. ( Cancer Sci 2008; 99: 2417–2427)