TY - JOUR
T1 - Inhibition of tumor growth and enhancement of metastasis after transfection of the γ-interferon gene
AU - Lollini, P. L.
AU - Bosco, M. C.
AU - Cavallo, F.
AU - De Giovanni, C.
AU - Giovarelli, M.
AU - Landuzzi, L.
AU - Musiani, P.
AU - Modesti, A.
AU - Nicoletti, G.
AU - Palmieri, G.
AU - Santoni, A.
AU - Young, H. A.
AU - Forni, G.
AU - Nanni, P.
PY - 1993
Y1 - 1993
N2 - Cells from the spontaneous metastatic TS/A mammary adenocarcinoma of a BALB/c mouse were transfected with the murine γ-interferon (IFN-γ) gene. Six clones (IFN-γ clones) releasing between 2 and 6,000 international units (IU) of IFN-γ/ml culture medium, were compared to TS/A parental cells (TS/A-pc) and to cells transfected with neomycin resistance gene only (NEO cells). Autocrine IFN-γ up-regulated membrane expression of H-2 class-I and Ly-6 glycoproteins, but did not alter cellular proliferation in vitro. All IFN-γ clones gave rise to progressive tumors with a growth rate significantly slower than that of tumors induced by TS/A-pc and NEO cells, and inversely correlated with the amount of IFN-γ secreted. TS/A-pc and NEO tumors displayed a marginal reactive infiltrate, whereas those formed by IFN-γ clones were massively infiltrated mostly by macrophages. In T- and NK-deficient mice the growth of tumors formed by IFN-γ clones was not enhanced. In vitro tests showed that IFN-γ clone cells were markedly more lysed by macrophages than TS/A-pc and NEO cells, while they remained poorly sensitive to NK and LAK cells. These data as a whole suggest that the development of solid tumors by IFN-γ clones is primarily hampered by macrophages and not by T-lymphocytes or NK cells. When spontaneous metastatic ability was compared, 2 IFN-γ clones releasing 2-4 IFN-γ IU/ml were significantly more metastatic, while most IFN-γ clones appeared to be as metastatic as NEO cells. By contrast, following intravenous challenge, all IFN-γ clones produced 5-10 times more experimental metastases than NEO cells. The higher metastatic ability of IFN-γ clones was attributed to increased resistance to NK cells since, in NK-depleted BALB/c mice, metastatic spread of IFN-γ clones was not enhanced, whereas a 50-fold increase in the number of metastases was found upon injection of NEO cells.
AB - Cells from the spontaneous metastatic TS/A mammary adenocarcinoma of a BALB/c mouse were transfected with the murine γ-interferon (IFN-γ) gene. Six clones (IFN-γ clones) releasing between 2 and 6,000 international units (IU) of IFN-γ/ml culture medium, were compared to TS/A parental cells (TS/A-pc) and to cells transfected with neomycin resistance gene only (NEO cells). Autocrine IFN-γ up-regulated membrane expression of H-2 class-I and Ly-6 glycoproteins, but did not alter cellular proliferation in vitro. All IFN-γ clones gave rise to progressive tumors with a growth rate significantly slower than that of tumors induced by TS/A-pc and NEO cells, and inversely correlated with the amount of IFN-γ secreted. TS/A-pc and NEO tumors displayed a marginal reactive infiltrate, whereas those formed by IFN-γ clones were massively infiltrated mostly by macrophages. In T- and NK-deficient mice the growth of tumors formed by IFN-γ clones was not enhanced. In vitro tests showed that IFN-γ clone cells were markedly more lysed by macrophages than TS/A-pc and NEO cells, while they remained poorly sensitive to NK and LAK cells. These data as a whole suggest that the development of solid tumors by IFN-γ clones is primarily hampered by macrophages and not by T-lymphocytes or NK cells. When spontaneous metastatic ability was compared, 2 IFN-γ clones releasing 2-4 IFN-γ IU/ml were significantly more metastatic, while most IFN-γ clones appeared to be as metastatic as NEO cells. By contrast, following intravenous challenge, all IFN-γ clones produced 5-10 times more experimental metastases than NEO cells. The higher metastatic ability of IFN-γ clones was attributed to increased resistance to NK cells since, in NK-depleted BALB/c mice, metastatic spread of IFN-γ clones was not enhanced, whereas a 50-fold increase in the number of metastases was found upon injection of NEO cells.
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M3 - Article
C2 - 8370628
AN - SCOPUS:0027490205
VL - 55
SP - 320
EP - 329
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -