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Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1. However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis. We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice. Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.
Pubmed ID: 31578522
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Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsA fungal rDNA internal transcribed spacer (ITS) sequence database (although additional genes and genetic markers are also welcome) to facilitate identification of environmental samples of fungal DNA. Additional important features include user annotation of INSD sequences to add metadata on, e.g., locality, habitat, soil, climate, and interacting taxa. The user can furthermore annotate INSD sequences with additional species identifications that will appear in the results of any analyses done. UNITE focuses on high-quality ITS sequences generated from fruiting bodies collected and identified by experts and deposited in public herbaria. In addition, it also holds all fungal ITS sequences in the International Nucleotide Sequence Databases (INSD: NCBI, EMBL, DDBJ). Both sets of sequences may be used in any analyses carried out. UNITE is accompanied by a project management system called PlutoF, where users can store field data, document the sequencing lab procedures, manage sequences, and make analyses. PlutoF intends to make it possible for taxonomists, ecologists, and biogeographers to use a common platform for data storage, handling, and analyses, with the intent of facilitating an integration of these disciplines. A user can have an unlimited number of projects but still make analyses across any project data available to him.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 23,2023.Software package for comparison and analysis of microbial communities, primarily based on high-throughput amplicon sequencing data, but also supporting analysis of other types of data. QIMME analyzes and transforms raw sequencing data generated on Illumina or other platforms to publication quality graphics and statistics.
View all literature mentionsOrdination methods, diversity analysis and other functions for community and vegetation ecologists.
View all literature mentionsSoftware for handling and analysis of high-throughput microbiome census data.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsA unified data repository of the National Cancer Institute (NCI)'s Genomic Data Commons (GDC) that enables data sharing across cancer genomic studies in support of precision medicine. The GDC supports several cancer genome programs at the NCI Center for Cancer Genomics (CCG), including The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI). The GDC Data Portal provides a platform for efficiently querying and downloading high quality and complete data. The GDC also provides a GDC Data Transfer Tool and a GDC API for programmatic access.
View all literature mentionsSoftware versatile open source tool for metagenomics. Used for processing and preparing metagenomics, genomics and population genomics nucleotide sequence data.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
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