Abstract |
A mutein, F4168, of human tumor necrosis factor alpha (hTNF-alpha) containing the cell-adhesive Arg-Gly-Asp (RGD) sequence near the N terminus was constructed. In contrast to hTNF-alpha, the mutein had binding activity to B16F10/L5 melanoma cells similar to that of fibronectin or laminin, indicating that the adhesive nature of the RGD sequence is conferred upon hTNF-alpha. Introduction of the RGD sequence did not alter the antitumor potential of hTNF-alpha. Simultaneous injection of F4168 and B16F10/L5 melanoma cells into mice did not enhance metastasis formation in lungs, whereas hTNF-alpha significantly promoted it. Enhancement of spontaneous lymph node metastasis of B16F10/L5 cells was also evident in TNF-alpha- but not in F4168-treated mice. In the spontaneous lymph node metastasis model of MethA fibrosarcoma, F4168 injection inhibited metastasis formation more effectively than hTNF-alpha. B16F10/L5 melanoma cells treated with hTNF-alpha enhanced not only their binding activity to laminin but also their invasive potential into Matrigel, whereas F4168 showed no such enhancement. These results suggest that F4168 is a low-toxicity mutein of hTNF-alpha.
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Authors | K Miyata, Y Mitsuishi, H Shikama, K Kuroda, K Nishimura, N Sakae, M Kato |
Journal | Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
(J Interferon Cytokine Res)
Vol. 15
Issue 2
Pg. 161-9
(Feb 1995)
ISSN: 1079-9907 [Print] United States |
PMID | 8590320
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- F 4168
- Oligopeptides
- Recombinant Fusion Proteins
- Tumor Necrosis Factor-alpha
- arginyl-glycyl-aspartic acid
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Topics |
- Amino Acid Sequence
- Animals
- Base Sequence
- Cell Adhesion
- Cell Death
- Fibrosarcoma
(secondary)
- Humans
- Lung Neoplasms
(secondary)
- Lymphatic Metastasis
- Melanoma, Experimental
(pathology, secondary)
- Mice
- Molecular Sequence Data
- Mutagenesis, Insertional
- Neoplasm Metastasis
- Oligopeptides
(genetics, physiology)
- Recombinant Fusion Proteins
(genetics, physiology)
- Skin Neoplasms
(secondary)
- Tumor Cells, Cultured
- Tumor Necrosis Factor-alpha
(genetics, immunology, metabolism, physiology)
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