Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells.
We identified a thymosin-beta4 gene overexpression in malignant mouse fibrosarcoma cells (QRsP-30) that were derived from clonal weakly tumorigenic and nonmetastatic QR-32 cells by using a differential display method. Thymosin-beta4 is known as a 4.9-kd polypeptide that interacts with G-actin and functions as a major actin-sequestering protein in cells. All of the six malignant fibrosarcoma cell lines that have been independently converted from QR-32 cells expressed high levels of thymosin-beta4 mRNA and its expression in tumor cells was correlated with tumorigenicity and metastatic potential. Up-regulation of thymosin-beta4 in QR-32 cells (32-S) transfected with sense thymosin-beta4 cDNA converted the cells to develop tumors and formed numerous lung metastases in syngeneic C57BL/6 mice. In contrast, antisense thymosin-beta4 cDNA-transfected QRsP-30 (30-AS) cells reduced thymosin-beta4 expression, and significantly lost tumor formation and metastases to distant organs. Vector-alone transfected cells (32-V or 30-V cells) behaved like their parental cells. We observed that tumor cell motility, cell shape, and F-actin organization is regulated in proportion to the level of thymosin-beta4 expression. These findings indicate that thymosin-beta4 molecule regulates fibrosarcoma cell tumorigenicity and metastasis through actin-based cytoskeletal organization.
Kobayashi
Tokushige
T
Division of Cancer Pathobiology, Research Section of Pathophysiology, Hokkaido University, Sapporo, Japan.
Okada
Futoshi
F
Fujii
Nobuyuki
N
Tomita
Naoko
N
Ito
Satoru
S
Tazawa
Hiroshi
H
Aoyama
Tetsuya
T
Choi
Sung Ki
SK
Shibata
Toshiyuki
T
Fujita
Hisakazu
H
Hosokawa
Masuo
M
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013947:Thymosin / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099201:Thymosin beta(4)
D013947:Thymosin; D000099201:Thymosin beta(4)