Table 4 Summary of in vivo studies investigating bisphosphonate effects on macrophages.
From: Tumour macrophages as potential targets of bisphosphonates
Model | Bisphosphonate | Main Findings | Reference |
|---|---|---|---|
BALB-neut mice with mammary tumour virus (rat c-erb-2-neu/transgene) | ZOL 0.1 mg/kg or PAM 2 mg/kg 5 days a week. | Zol decreased macrophage infiltration into tumour stroma associated with decreased levels of pro-MMP-9 and VEGF | Melani C et al [21] |
Mammary carcinoma cells implanted in BALB-neutT mice | ZOL 100 μM/kg Once a week for 4 weeks, followed by 3 weeks rest, cycle continued. | Impaired TAM recruitment and infiltration into tumour and reduced neo-vascularisation reversal of TAM polarity from pro-tumoural M2 to tumoricidal M1 | Coscia et al [83] |
HARA-B lung cancer cells implanted in BALB/c nude mice | Clodrolip 200 μL or 400 μL Every 3 days for 6 weeks (s.c.). | Reduced TAM infiltration correlated to reduced metastatic spread | Hiraoka et al [85] |
Human melanoma cell line IIB-MEL-J with or without MCP-1 expression vector. Athymic male NIC-(S)-Nu mice | Clodrolip 50 μl or 200 μl (6 mg clodronate per 1 ml ) From day before cell injection and every 5 to 7 days thereafter. | Reduced TAMs infiltration correlated to decreased tumour volume and angiogenesis and increased survival | Gazzangia et al [86] |
F9 teratocarcinoma cells implanted in SV129 female mice | Clodrolip, 1 mg/20 g every 4 days. | Reduced TAM infiltration. 82% reduction in tumour volume | Zeisberger et al [87] |
A673 rhabdomyosarcoma cells into CD-1 nude mice | Clodrolip, 1 mg/20 g every 4 days. | 93% reduction in TAM 89% reduction in blood vessel density | Zeisberger et al [87] |
Metastatic liver cancer Mouse model LM3R or SMMC7721 human hepatocellular cell lines in BALB/c nu/nu mice | Clodrolip 100 μg/kg 3 times a week or, ZOL 100 μg/kg 3 times a week and or 30 mg/kg sorafenib. | Reduced TAM infiltration with combination therapy. Correlated with decreased tumour growth, angiogenesis and lung metastasis. ZOL had greater effect than clodrolip | Zhang et al [88] |
Cervical carcinoma K14-HPV16 transgenic mice | ZOL 100 μg Every day for 3 months. | Decreased MMP-9 expression by TAMs | Giraudo et al [72] |
Peritoneal macrophage obtained from CBA-J mice injected with AC29 mesothelioma cells | Clodronate 200 μl twice over 10 days. | Depleted peritoneal macrophages. Decreased tumour growth | Veltman et al [89] |
CBA-J mice injected with AC29 mesothelioma cells | ZOL 100 μg/kg s.c. Every day for 25 days. | Increased myeloid precursors. Decreased TAMs No significant increase in survival or decrease in tumour burden | Veltman et al [89] |