Colonization of experimental murine breast tumours by Escherichia coli K-12 significantly alters the tumour microenvironment.
The successful application of live bacteria in cancer therapy requires a more detailed understanding of bacterial interaction with the tumour microenvironment. Here, we analysed the effect of Escherichia coli K-12 colonization on the tumour microenvironment by immunohistochemistry and fluorescence microscopy in the murine 4T1 breast carcinoma model. We described the colonization of tumour-bearing mice, as well as the spatiotemporal distribution of E. coli K-12 in the 4T1 tumour tissue over a period of 14 days. The colonization resulted within 3 days in large avascular necrotic tissue, redistribution of hypoxic areas and an enhanced collagen IV deposition within the colonized tumour tissue, which changed the tumoral perfusion of systemically injected immunoglobulins. In addition, E. coli K-12 colonization led to the redistribution of tumour-associated macrophages, forming a granulation tissue around bacterial colonies, and also to an increase in TNFalpha and matrix metalloproteinase 9 expression. Colonization of 4T1 tumours by E. coli K-12 resulted in strong reduction of pulmonary metastatic events. These new insights will contribute to the general understanding of the tumour-microbe cross-talk and to the design of bacterial strains with enhanced anticancer efficiency.
Weibel
Stephanie
S
Department of Microbiology, Biocenter, University of Wuerzburg, 97074 Wuerzburg, Germany.
Stritzker
Jochen
J
Eck
Matthias
M
Goebel
Werner
W
Szalay
Aladar A
AA
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000378:metabolism; D015169:Colony Count, Microbial; D048168:Escherichia coli K12 / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000382:microbiology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008264:Macrophages / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009336:Necrosis / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D024141:Collagen Type IV; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D010100:Oxygen