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Carcinogenesis Advance Access originally published online on July 19, 2006
Carcinogenesis 2006 27(12):2434-2441; doi:10.1093/carcin/bgl069
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs

Xian-cheng Chen1,2,{dagger}, Rui Wang1,{dagger}, Xia Zhao2, Yu-quan Wei1,*, Min Hu1, Yang-sheng Wang1, Xiao-wei Zhang1, Ru Zhang1, Lin Zhang1, Bin Yao1, Lian Wang1, Yong-qian Jia1, Ting-ting Zeng1, Jin-liang Yang1, Ling Tian1, Bing Kan1, Xiao-juan Lin2, Song Lei1, Hong-xin Deng1, Yan-jun Wen1, Yong-qiu Mao1 and Jiong Li1

1 National Key Laboratory of Biotherapy and Cancer Center, West China Hospital Guo Xue Xian No. 37, Chengdu, Sichuan 610041, People's Republic of China
2 Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University Guo Xue Xian No. 37, Chengdu, Sichuan 610041, People's Republic of China

*To whom correspondence should be addressed. Fax: +86 28 85250731; Email: yuquawei{at}vip.sina.com or xia-zhao{at}126.com

Mesenchymal stem cells (MSCs) were adenovirally engineered to secrete interleukin-12 (AdIL-12-MSCs) and evaluated for their anticarcinogenesis efficacy against three kinds of unestablished tumor models including B16 melanoma, LLC Lewis lung cancer and HCC hepatoma. Injection of AdIL-12-MSCs into protected mice before tumor inoculation prevented all of 12 mice in B16 preventive groups, 10 out of 12 in LLC lung cancer model and 11 out of 12 mice in HCC hepatoma model from developing tumors, whereas the control groups pre-receiving PBS were validated for 100% carcinogenesis; the tumor formation rates in free-AdIL-12 and vacant MSC groups were unveiled between ~83 and 100% even with plentiful angiogenesis and newborn lymphatic vessels, as well as distant metastases. As a novel approach, AdIL-12-MSC has revealed expected preventive effects on carcinogenesis (P < 0.01) with low-toxic, broad-spectrum and long-range superiorities. In conclusion, our data indicate that AdIL-12-MSC possess the potential for tropism to preclinical tumor lesions and deprives surviving or hibernating tumor cells, which have escaped from conventional treatments, of revival and recurrence.


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