Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice
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Shinji Miwa1,2,3, Shuya Yano1,2, Yong Zhang1,2, Yasunori Matsumoto2, Fuminari Uehara1,2, Mako Yamamoto1,2, Yukihiko Hiroshima1,2, Hiroaki Kimura3, Katsuhiro Hayashi3, Norio Yamamoto3, Michael Bouvet2, Hiroyuki Tsuchiya3, Robert M. Hoffman1,2 and Ming Zhao1
1 AntiCancer, Inc.; San Diego, California USA
2 Department of Surgery; University of California, San Diego; San Diego, California USA
3 Department of Orthopedic Surgery; Kanazawa University Graduate School of Medical Sciences; Kanazawa, Ishikawa, Japan
Robert M. Hoffman, email:
Keywords: breast cancer, bone metastasis, GFP, RFP, bacterial therapy, Salmonella typhimurium A1-R
Received: July 1, 2014 Accepted: July 16, 2014 Published: July 16, 2014
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.
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