Dataset Information

Exploring the Role of the Gut and Intratumoral Microbiomes in Tumor Progression and Metastasis.

ABSTRACT: Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases. In this review, we highlight the role of the intratumoral and gut microbiomes in cancer cell invasion, migration, and metastatic ability and outline the potential options for microbiota modulation. As shown in murine models, probiotics inhibited tumor development, reduced tumor volume, and suppressed angiogenesis and metastasis. Moreover, modulation of an unfavorable microbiome might improve efficacy and reduce treatment-related toxicities, bringing clinical benefit to patients with metastatic cancer.

SUBMITTER: Sevcikova A

PROVIDER: S-EPMC10742837 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Exploring the Role of the Gut and Intratumoral Microbiomes in Tumor Progression and Metastasis.

Sevcikova Aneta A Mladosievicova Beata B Mego Michal M Ciernikova Sona S

International journal of molecular sciences 20231206 24

Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and i ...[more]

PMID: 38139030

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Project description:There is a growing awareness that tumor-adjacent normal tissues used as control samples in cancer studies do not represent fully healthy tissues. Instead, they are intermediates between healthy tissues and tumors. The factors that contribute to the deviation of such control samples from healthy state include exposure to the tumor-promoting factors, tumor-related immune response, and other aspects of tumor microenvironment. Characterizing the relation between gene expression of tumor-adjacent control samples and tumors is fundamental for understanding roles of microenvironment in tumor initiation and progression, as well as for identification of diagnostic and prognostic biomarkers for cancers. To address the demand, we developed and validated TranNet, a computational approach that utilizes gene expression in matched control and tumor samples to study the relation between their gene expression profiles. TranNet infers a sparse weighted bipartite graph from gene expression profiles of matched control samples to tumors. The results allow us to identify predictors (potential regulators) of this transition. To our knowledge, TranNet is the first computational method to infer such dependencies. We applied TranNet to the data of several cancer types and their matched control samples from The Cancer Genome Atlas (TCGA). Many predictors identified by TranNet are genes associated with regulation by the tumor microenvironment as they are enriched in G-protein coupled receptor signaling, cell-to-cell communication, immune processes, and cell adhesion. Correspondingly, targets of inferred predictors are enriched in pathways related to tissue remodelling (including the epithelial-mesenchymal Transition (EMT)), immune response, and cell proliferation. This implies that the predictors are markers and potential stromal facilitators of tumor progression. Our results provide new insights into the relationships between tumor adjacent control sample, tumor and the tumor environment. Moreover, the set of predictors identified by TranNet will provide a valuable resource for future investigations.

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Dataset Information

Exploring the Role of the Gut and Intratumoral Microbiomes in Tumor Progression and Metastasis.

Publications

Exploring the Role of the Gut and Intratumoral Microbiomes in Tumor Progression and Metastasis.

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