shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression志贺氏杆菌介导巨噬细胞在小鼠乳腺癌的损耗与肿瘤相关的回归模型.pdfVIP

Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression 1.¤a 1,2. 1¤b 3 Katharina Galmbacher , Martin Heisig , Christian Hotz , Joerg Wischhusen , Antoine Galmiche1¤c, Birgit Bergmann1,2, Ivaylo Gentschev1¤d, Werner Goebel2¤e, Ulf R. Rapp1¤f, Joachim 1 ¤g Fensterle * ¨ ¨ ¨ ¨ ¨ ¨ ¨ 1 Institut fur Medizinische Strahlenkunde und Zellforschung, Universitat Wurzburg, Wurzburg, Germany, 2 Institut fur Mikrobiologie, Biozentrum, Universitat Wurzburg, ¨ ¨ ¨ ¨ Wurzburg, Germany, 3 Universitatsfrauenklinik Wurzburg, Wurzburg, Germany Abstract A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs) represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDaroA) and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigell