Dataset Information

Patterns of Tumor Progression Predict Small and Tissue-Specific Tumor-Originating Niches.

ABSTRACT: The development of cancer is a multistep process in which cells increase in malignancy through progressive alterations. Such altered cells compete with wild-type cells and have to establish within a tissue in order to induce tumor formation. The range of this competition and the tumor-originating cell type which acquires the first alteration is unknown for most human tissues, mainly because the involved processes are hardly observable, aggravating an understanding of early tumor development. On the tissue scale, one observes different progression types, namely with and without detectable benign precursor stages. Human epidemiological data on the ratios of the two progression types exhibit large differences between cancers. The idea of this study is to utilize data of the ratios of progression types in human cancers to estimate the homeostatic range of competition in human tissues. This homeostatic competition range can be interpreted as necessary numbers of altered cells to induce tumor formation on the tissue scale. For this purpose, we develop a cell-based stochastic model which is calibrated with newly-interpreted human epidemiological data. We find that the number of tumor cells which inevitably leads to later tumor formation is surprisingly small compared to the overall tumor and largely depends on the human tissue type. This result points toward the existence of a tissue-specific tumor-originating niche in which the fate of tumor development is decided early and long before a tumor becomes detectable. Moreover, our results suggest that the fixation of tumor cells in the tumor-originating niche triggers new processes which accelerate tumor growth after normal tissue homeostasis is voided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. For other tissues, our results might aid to identify the tumor-originating cell type. For instance, data on primary and secondary glioblastoma suggest that the tumors originate from a cell type competing in a range of 300 - 1,900 cells.

SUBMITTER: Buder T

PROVIDER: S-EPMC6335293 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Patterns of Tumor Progression Predict Small and Tissue-Specific Tumor-Originating Niches.

Buder Thomas T Deutsch Andreas A Klink Barbara B Voss-Böhme Anja A

Frontiers in oncology 20190110

The development of cancer is a multistep process in which cells increase in malignancy through progressive alterations. Such altered cells compete with wild-type cells and have to establish within a tissue in order to induce tumor formation. The range of this competition and the tumor-originating cell type which acquires the first alteration is unknown for most human tissues, mainly because the involved processes are hardly observable, aggravating an understanding of early tumor development. On ...[more]

PMID: 30687642

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Project description:BACKGROUND: Mytilus species are important in marine ecology and in environmental quality assessment, yet their molecular biology is poorly understood. Molecular aspects of their reproduction, hybridisation between species, mitochondrial inheritance, skewed sex ratios of offspring and adaptation to climatic and pollution factors are priority areas. METHODOLOGY/PRINCIPAL FINDINGS: To start to address this situation, expressed genetic transcripts from M. galloprovincialis were pyrosequenced. Transcripts were isolated from the digestive gland, foot, gill and mantle of both male and female mussels. In total, 175,547 sequences were obtained and for foot and mantle, 90% of the sequences could be assembled into contiguous fragments but this reduced to 75% for the digestive gland and gill. Transcripts relating to protein metabolism and respiration dominated including ribosomal proteins, cytochrome oxidases and NADH dehydrogenase subunits. Tissue specific variation was identified in transcripts associated with mitochondrial energy metabolism, with the digestive gland and gill having the greatest transcript abundance. Using fragment recruitment it was also possible to identify sites of potential small RNAs involved in mitochondrial transcriptional regulation. Sex ratios based on Vitelline Envelop Receptor for Lysin and Vitelline Coat Lysin transcript abundances, indicated that an equal sex distribution was maintained. Taxonomic profiling of the M. galloprovincialis tissues highlighted an abundant microbial flora associated with the digestive gland. Profiling of the tissues for genes involved in intermediary metabolism demonstrated that the gill and digestive gland were more similar to each other than to the other two tissues, and specifically the foot transcriptome was most dissimilar. CONCLUSIONS: Pyrosequencing has provided extensive genomic information for M. galloprovincialis and generated novel observations on expression of different tissues, mitochondria and associated microorganisms. It will also facilitate the much needed production of an oligonucleotide microarray for the organism.

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Dataset Information

Patterns of Tumor Progression Predict Small and Tissue-Specific Tumor-Originating Niches.

Publications

Patterns of Tumor Progression Predict Small and Tissue-Specific Tumor-Originating Niches.

Similar Datasets

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