Microbiome and Colorectal Carcinoma

Tlaskalová‐Hogenová, Helena; Vannucci, Luca; Klimešová, Klára; Štěpánková, Renata; Křižan, J; Kverka, Miloslav

doi:10.1097/ppo.0000000000000052

Cited by 50 publications

(19 citation statements)

References 115 publications

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“…This finding may indicate that an inflammatory environment could promote in vivo CRC tumor growth. Previous studies have demonstrated that inflammatory processes are associated with CRC tumorigenesis [47][48][49], and that the microbiota has the potential to shape the inflammatory microenvironment in the intestine [50].…”

Section: Discussionmentioning

confidence: 99%

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Larsson

Ljuslinder

et al. 2020

Cancers

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Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Larsson

Ljuslinder

et al. 2020

Cancers

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“…Notably, Swidsinski et al demonstrated the relationship between abundance of E. coli and CRC tumorigenesis early in 1998[ 27 ]. It is conceivable that intestinal microbiota plays a key role in the beginning of CRC with mounting evidence [ 28 – 31 ]. According to what had been founded in NCM460 and HCT116 cell lines, we suspected that in APC mutation population, ethanol was a risk factor for development of colorectal cancer, which might contribute to allowing gram-negative bacteria LPS into the blood, and activate TLR4/NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Adenomatous polyposis coligenotype-dependent toll-like receptor 4 activity in colon cancer

et al. 2016

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Toll-like receptors (TLRs)/NF-κB activation stimulated by lipopolysaccharide (LPS) was associated with diverse biological response in colon cancer, but the underlying mechanism was largely unknown. In the current study, we reported cell proliferation was elevated in adenomatous polyposis coli (APC) mutated- and APC knockdown cell lines, while the proliferation was inhibited in APC wild-type cell lines. Besides, in vivo experiments showed that LPS promoted APC knockdown tumor growth while inhibited proliferation of APC wild type. Further study confirmed that activation of TLRs/NF-κB signaling pathway by LPS cross regulated with APC/GSK-3β/β-catenin pathway, which were depend on APC status of cell lines. Taken together, APC genotypes play a key role in LPS induced different colon cancer biological response by cross-regulating β-catenin and NF-κB, which may provide a novel strategy for carcinogenesis prevention.

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“…It is generally accepted that the gut microbiome plays a role in CRC development. Experimental proof of gut microbiota involvement in CRC development came from gnotobiotic animal models ( Reddy et al, 1975 ; Vannucci et al, 2008 ; Arthur and Jobin, 2011 ; Klimesova et al, 2013 ; Tlaskalova-Hogenova et al, 2014 ). Recent studies using next generation sequencing and polymerase chain reaction have shown that Fusobacterium nucleatum is frequently detected in stool and biopsy samples from CRC patients ( Castellarin et al, 2012 ; Kostic et al, 2012 ; Flanagan et al, 2014 ).…”

Section: Oral Microbiota and Colorectal Carcinogenesismentioning

confidence: 99%

Oral Bacterial and Fungal Microbiome Impacts Colorectal Carcinogenesis

2018

Self Cite

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Host’s physiology is significantly influenced by microbiota colonizing the epithelial surfaces. Complex microbial communities contribute to proper mucosal barrier function, immune response, and prevention of pathogen invasion and have many other crucial functions. The oral cavity and large intestine are distant parts of the digestive tract, both heavily colonized by commensal microbiota. Nevertheless, they feature different proportions of major bacterial and fungal phyla, mostly due to distinct epithelial layers organization and different oxygen levels. A few obligate anaerobic strains inhabiting the oral cavity are involved in the pathogenesis of oral diseases. Interestingly, these microbiota components are also enriched in gut inflammatory and tumor tissue. An altered microbiota composition – dysbiosis – and formation of polymicrobial biofilms seem to play important roles in the development of oral diseases and colorectal cancer. In this review, we describe the differences in composition of commensal microbiota in the oral cavity and large intestine and the mechanisms by which microbiota affect the inflammatory and carcinogenic response of the host.

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Microbiome and Colorectal Carcinoma

Cited by 50 publications

References 115 publications

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells

Adenomatous polyposis coligenotype-dependent toll-like receptor 4 activity in colon cancer

Oral Bacterial and Fungal Microbiome Impacts Colorectal Carcinogenesis

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