RT Journal Article
SR Electronic
T1 Patterns of tumor progression predict small and tissue-specific tumor-originating niches
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 330175
DO 10.1101/330175
A1 Thomas Buder
A1 Andreas Deutsch
A1 Barbara Klink
A1 Anja Voss-Böhme
YR 2018
UL http://biorxiv.org/content/early/2018/05/25/330175.abstract
AB Cancer development is a multistep process in which cells increase in malignancy through progressive alterations. The early phase of this process is hardly observable which aggravates an understanding of later tumor development. We shed light on this initial phase with a cell-based stochastic model calibrated with epidemiological data from the tissue scale. Our model allows to estimate the number of tumor cells needed for tumor formation in human tissues based on data on the diagnosed ratios of benign and malignant tumors. We find that the minimal number of cells needed for tumor formation is surprisingly small and largely depends on the tissue type. Our results point towards the existence of tumor-originating niches in which the fate of tumor development is early decided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. Our estimates might help to identify the tumor-originating cell type, e.g. our analysis suggests for glioblastoma that the tumors originate from a cell type competing in a range of 300 - 1900 cells.Summary We estimate the number of tumor cells needed for tumor formation in human tissues and propose the existence of small and tissue-specific tumor-originating niches which might help to find tumor-originating cell types, in particular in glioblastoma.