Abstract
Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.
Highlights
Bone metastasis is found in more than 80% of patients in advanced stages of breast cancer [1] and is highly treatment resistant and results in extreme pain and high mortality
We have shown that S. typhimurium A1-R can target chemo-resistant pancreatic cancer stem-like cells [16] and pancreatic cancer patient-derived orthotopic xenograft (PDOX) models [17,18,19]
Typhimurium A1-R can prevent human breast cancer bone metastasis using a metastatic variant in nude mouse models
Summary
Bone metastasis is found in more than 80% of patients in advanced stages of breast cancer [1] and is highly treatment resistant and results in extreme pain and high mortality. Typhimurium A1-R can prevent human breast cancer bone metastasis using a metastatic variant in nude mouse models. Fluorescence imaging demonstrated that S. typhimurium A1-R expressing GFP selectively invaded and replicated intracellularly in the MDA-MB-435 cells expressing RFP (Fig. 1a). After injection of S. typhimurium A1-R (5×107 CFU, i.v.) to non-tumor-bearing nude mice, blood, spleen, and bone marrow were cultured on Luria-Bertani (LB) agar (Fig. 2a).
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