Abstract |
The interaction of tumor cells with the basement membrane plays a crucial role in tumor metastasis. VLA-6 ( alpha6beta1) integrin is one of the major surface receptors for the basement membrane, specifically recognizing laminin. To study the role of VLA-6 integrin in tumor invasion and metastasis, we synthesized a ribozyme that selectively degrades the integrin alpha6 subunit mRNA. The catalytic activity of the ribozyme was verified by in vitro cleavage of alpha6 subunit mRNA. Introduction of the anti-alpha6 ribozyme gene into the human fibrosarcoma cell line HT1080 yielded stable transfectants, which expressed a significantly reduced level of integrin alpha6 mRNA. Flow cytometric analysis showed that the surface expression of VLA-6, but not other integrins, was reduced by approximately 70% in transfected cells. Ribozyme-transfected cells were less adherent to laminin-coated substrata and less invasive into reconstituted basement membrane than mock-transfected cells. When injected i.v. into nude mice, ribozyme-transfected cells produced no lung metastasis in all except 1 of 35 mice, though mock-transfected cells produced multiple lung metastases in 22 of 29 mice. Our results indicate that VLA-6 integrin plays a critical role in tumor invasion and metastasis and may serve as a potential target for eradication of tumor metastasis in the lung.
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Authors | H Yamamoto, A Irie, Y Fukushima, T Ohnishi, N Arita, T Hayakawa, K Sekiguchi |
Journal | International journal of cancer
(Int J Cancer)
Vol. 65
Issue 4
Pg. 519-24
(Feb 08 1996)
ISSN: 0020-7136 [Print] United States |
PMID | 8621237
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Integrin alpha6
- RNA, Catalytic
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Topics |
- Animals
- Antigens, CD
(genetics, physiology)
- Base Sequence
- Cell Adhesion
- Female
- Fibrosarcoma
(pathology)
- Humans
- Integrin alpha6
- Lung Neoplasms
(secondary)
- Mice
- Mice, Inbred BALB C
- Molecular Sequence Data
- Neoplasm Invasiveness
- Neoplasm Transplantation
- RNA, Catalytic
(pharmacology)
- Transplantation, Heterologous
- Tumor Cells, Cultured
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