Platelet Factor 4 Gene Transfection into Tumor Cells Inhibits Angiogenesis, Tumor Growth and Metastasis

• Published in: Anticancer research 2005-03, Vol.25 (2A), p.847-851
• Main Authors: YAMAGUCHI, Kentaro, OGAWA, Kenji, KATSUBE, Takao, SHIMAO, Kazuya, KONNO, Soichi, SHIMAKAWA, Takeshi, YOSHIMATSU, Kazuhiko, NARITAKA, Yoshihiko, YAGAWA, Hirokazu, HIROSE, Kunitaka
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carcinoma, Lewis Lung - blood supply; Carcinoma, Lewis Lung - genetics; Carcinoma, Lewis Lung - pathology; Carcinoma, Lewis Lung - therapy; Cell Growth Processes - physiology; Humans; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - therapy; NIH 3T3 Cells; Platelet Factor 4 - biosynthesis; Platelet Factor 4 - genetics; Transfection; Tumors
• ISSN: 0250-7005; 1791-7530

Tumor growth and metastasis depend on angiogenesis, which is triggered by a chemical signal from the tumor cells to resting endothelial cells which then enter into a phase of rapid growth. Platelet Factor 4 (PF4) inhibits endothelial proliferation in vitro and angiogenesis in vivo. PF4 also inhibits tumor growth, however, as with other angiogenesis inhibitors, sustained tumor growth inhibition requires prolonged exposure to the recombinant protein. In this study, Lewis lung carcinoma (LLH) cells were transfected with the human PF4 via mammalian expression vectors and the ability of the transfected cells to form tumors and metastasis in vivo was evaluated. To evaluate the tumor growth rate of PF4-transfected (LLH/PF4) or control (LLH/neo) cells in vivo, we injected LLH/PF4 or LLH/neo cells subcutaneously (s.c.) or intravenously (i.v.). In the s.c. assay, LLH/PF4 had no significant effect on tumor growth. Conversely, in the i.v. assay, PF4 significantly reduced the number of lung metastasis (p=0.019) and weight (p=0.056). The inhibition of lung metastasis suggests that PF4 may inhibit tumor-associated neovascularization, and may prevent the affinity of tumor cells for the normal lung tissue.