Research Papers:
Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice
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Abstract
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
Correspondence:
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
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.
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