PURPOSE: Pro-interleukin-16 (pro-IL-16) is the precursor to mature interleukin-16 (IL-16) protein. Previous studies have demonstrated that pro-IL-16 can function as a regulator of cell cycle. A number of human T-cell leukemia and lymphoma cell lines are pro-IL-16 deficient. Intracellular expression of pro-IL-16 causes these cell lines to become quiescent, implicating loss of pro-IL-16 as a contributory step in T-cell malignancy. Therefore, we tested whether or not reintroduction of pro-IL-16 into solid tumors in mice could halt tumor growth. METHODS: MOLT-4 lymphoblastic leukemia cells were stably transfected with a dsRed-tomato virus and were injected subcutaneously into NOD/SCID/γ chain-knockout mice. Tumor growth was monitored with an in vivo imaging system. A pro-IL-16-GFP fusion virus or control GFP only virus was injected into the tumors, and mice were monitored for 1 week. RESULTS: Injection of the pro-IL-16-containing lentivirus inhibited growth of established MOLT-4 tumors in mice. Tumor explants exhibited diminished proliferative capacity. CONCLUSIONS: Our data support the concept that restoration of pro-IL-16 expression in malignant T cells may have therapeutic value.
PURPOSE:Pro-interleukin-16 (pro-IL-16) is the precursor to mature interleukin-16 (IL-16) protein. Previous studies have demonstrated that pro-IL-16 can function as a regulator of cell cycle. A number of humanT-cell leukemia and lymphoma cell lines are pro-IL-16 deficient. Intracellular expression of pro-IL-16 causes these cell lines to become quiescent, implicating loss of pro-IL-16 as a contributory step in T-cell malignancy. Therefore, we tested whether or not reintroduction of pro-IL-16 into solid tumors in mice could halt tumor growth. METHODS: MOLT-4 lymphoblastic leukemia cells were stably transfected with a dsRed-tomato virus and were injected subcutaneously into NOD/SCID/γ chain-knockout mice. Tumor growth was monitored with an in vivo imaging system. A pro-IL-16-GFP fusion virus or control GFP only virus was injected into the tumors, and mice were monitored for 1 week. RESULTS: Injection of the pro-IL-16-containing lentivirus inhibited growth of established MOLT-4 tumors in mice. Tumor explants exhibited diminished proliferative capacity. CONCLUSIONS: Our data support the concept that restoration of pro-IL-16 expression in malignant T cells may have therapeutic value.
Authors: P Mühlhahn; M Zweckstetter; J Georgescu; C Ciosto; C Renner; M Lanzendörfer; K Lang; D Ambrosius; M Baier; R Kurth; T A Holak Journal: Nat Struct Biol Date: 1998-08