Thymosin-β4 regulates motility and metastasis of malignant mouse fibrosarcoma cells

Tokushige Kobayashi, Futoshi Okada, Nobuyuki Fujii, Naoko Tomita, Satoru Ito, Hiroshi Tazawa, Tetsuya Aoyama, Sung Ki Choi, Toshiyuki Shibata, Hisakazu Fujita, Masuo Hosokawa

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109 Citations (Scopus)

Abstract

We identified a thymosin-β4 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-β4 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-β4 mRNA and its expression in tumor cells was correlated with tumorigenicity and metastatic potential. Up-regulation of thymosin-β4 in QR-32 cells (32-S) transfected with sense thymosin-β4 cDNA converted the cells to develop tumors and formed numerous lung metastases in syngeneic C57BL/6 mice. In contrast, antisense thymosin-β4 cDNA-transfected QRsP-30 (30-AS) cells reduced thymosin-β4 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-β4 expression. These findings indicate that thymosin-β4 molecule regulates fibrosarcoma cell tumorigenicity and metastasis through actin-based cytoskeletal organization.

Original languageEnglish
Pages (from-to)869-882
Number of pages14
JournalAmerican Journal of Pathology
Volume160
Issue number3
DOIs
Publication statusPublished - Jan 1 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kobayashi, T., Okada, F., Fujii, N., Tomita, N., Ito, S., Tazawa, H., Aoyama, T., Choi, S. K., Shibata, T., Fujita, H., & Hosokawa, M. (2002). Thymosin-β4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. American Journal of Pathology, 160(3), 869-882. https://doi.org/10.1016/S0002-9440(10)64910-3