Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2006-8-3
pubmed:abstractText
Inflammation associated with bacterial infections is a risk factor for cancers in humans, yet its role in breast cancer remains poorly understood. We have previously shown that innate immune inflammatory response against intestinal bacteria is sufficient to induce colon cancer. Here we report that infecting Rag2-deficient C57BL/6 Apc(Min/+) mice with an intestinal bacterial pathogen, Helicobacter hepaticus, significantly promotes mammary carcinoma in females and enhances intestinal adenoma multiplicity by a tumor necrosis factor alpha (TNFalpha)-dependent mechanism. The mammary and intestinal tumor development as well as the increase in proinflammatory mediators is suppressed by adoptive transfer of interleukin 10-competent CD4+CD45RB(lo)CD25+ regulatory (T(R)) cells. Furthermore, prior exposure of donor mice to H. hepaticus significantly enhances antitumor potency of their T(R) cells. Interestingly, these microbially experienced T(R) cells suppress tumorigenesis more effectively in recipient mice irrespective of their tumor etiology. These data suggest that infections with enteric pathogens enhance T(R)-cell potency and protect against epithelial cancers later in life, potentially explaining paradoxical increases in cancer risk in developed countries having more stringent hygiene practices. The possibility that dysregulated gut microbial infections in humans may lead to cancer in anatomically distant organs, such as breast, highlights the need for novel immune-based strategies in cancer prevention and treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7395-400
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16885333-Adenocarcinoma, pubmed-meshheading:16885333-Animals, pubmed-meshheading:16885333-DNA-Binding Proteins, pubmed-meshheading:16885333-Female, pubmed-meshheading:16885333-Helicobacter Infections, pubmed-meshheading:16885333-Helicobacter hepaticus, pubmed-meshheading:16885333-Immunity, Innate, pubmed-meshheading:16885333-Immunoglobulins, pubmed-meshheading:16885333-Immunotherapy, Adoptive, pubmed-meshheading:16885333-Interleukin-10, pubmed-meshheading:16885333-Intestinal Neoplasms, pubmed-meshheading:16885333-Mammary Neoplasms, Experimental, pubmed-meshheading:16885333-Mice, pubmed-meshheading:16885333-Mice, Inbred C57BL, pubmed-meshheading:16885333-Receptors, Interleukin-2, pubmed-meshheading:16885333-Recombinant Fusion Proteins, pubmed-meshheading:16885333-T-Lymphocytes, Regulatory, pubmed-meshheading:16885333-Tumor Necrosis Factor-alpha
pubmed:year
2006
pubmed:articleTitle
Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice.
pubmed:affiliation
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural