A mathematical model of tumour self-seeding reveals secondary metastatic deposits as drivers of primary tumour growth

@article{Scott2013AMM,
  title={A mathematical model of tumour self-seeding reveals secondary metastatic deposits as drivers of primary tumour growth},
  author={Jacob G. Scott and David Basanta and Alexander R. A. Anderson and Philip Gerlee},
  journal={Journal of The Royal Society Interface},
  year={2013},
  volume={10}
}
Two models of circulating tumour cell (CTC) dynamics have been proposed to explain the phenomenon of tumour ‘self-seeding’, whereby CTCs repopulate the primary tumour and accelerate growth: primary seeding, where cells from a primary tumour shed into the vasculature and return back to the primary themselves; and secondary seeding, where cells from the primary first metastasize into a secondary tissue and form microscopic secondary deposits, which then shed cells into the vasculature returning… 

Figures from this paper

Mathematical modelling of cancer invasion and metastatic spread
TLDR
A spatially explicit hybrid multi-organ metastasis modelling framework is developed that describes the invasive growth dynamics of individual cancer cells both at a primary site and at potential secondary metastatic sites in the body, as well as their transport from the primary to the secondary sites.
Computational Modelling of Metastasis Development in Renal Cell Carcinoma
TLDR
A mathematical model of spatial tumour growth is derived, confronted with experimental data of single metastatic tumours growth, and used to provide insights on the dynamics of multiple tumours growing in close vicinity to suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions.
An agent-based model of cancer stem cell initiated avascular tumour growth and metastasis: the effect of seeding frequency and location
TLDR
This work investigates stem cell seeding to an avascular tumour site using an agent-based stochastic model of breast cancer metastatic seeding and finds thatcell seeding rate and location are important features for tumour growth.
A Mathematical Framework for Modelling the Metastatic Spread of Cancer
TLDR
Using computational simulations, this model captures all the key steps of the invasion-metastasis cascade and supports the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs such as MMP-2.
A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer
TLDR
A first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade is created.
Model-based inference of metastatic seeding rates in de novo metastatic breast cancer reveals the impact of secondary seeding and molecular subtype
TLDR
It is found that dissemination rate through secondary seeding is up to 300 times higher than through primary seeding, which seems to be hormone receptor-independent, while that from the lungs to the brain appears HER2-independent.
A mathematical multi-organ model for bidirectional epithelial-mesenchymal transitions in the metastatic spread of cancer
TLDR
A first mathematical multi-organ model that explicitly accounts for EMT-processes in individual cancer cells in the context of the invasion-metastasis cascade is created.
Mechanistic mathematical modeling of glioma stem cell evolutionary dynamics and metastasis.
TLDR
A mathematical model of IDH-1 mutated secondary glioblastoma is developed using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolysis cells.
Mathematical modeling of tumor growth and metastatic spreading: validation in tumor-bearing mice.
TLDR
The data-based model development revealed several biologically significant findings, including the postulated link between primary tumor size and emission rate is validated and fast growing peritoneal metastases can only be described by such a complex partial differential equation model and not by ordinary differential equation models.
...
...

References

SHOWING 1-10 OF 37 REFERENCES
Tumor Self-Seeding by Circulating Cancer Cells
Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity.
TLDR
It is shown that therapy which fails to target the CSC population is not only unsuccessful in curing the patient, but also promotes malignant features in the recurring tumor, including rapid expansion, increased invasion, and enhanced heterogeneity.
Tumour evolution inferred by single-cell sequencing
TLDR
It is shown that with flow-sorted nuclei, whole genome amplification and next generation sequencing the authors can accurately quantify genomic copy number within an individual nucleus and indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
Cancer stem cells, self-seeding, and decremented exponential growth: theoretical and clinical implications.
TLDR
This essay will build a simple mathematical model from basic, experimentally-derived postulates and show how it could explain all of the classical features of epithelial breast cancer: histologic disorganization, rapid growth, large tumor size, angiogenesis, invasion, and metastasis.
Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer
TLDR
A silicon microfluidic cell-capture technology that, when coupled to an automated imaging system, enables the detection and enumeration of prostate cancer cells fished out from the blood, taking advantage of prostate-specific antigen (PSA), a unique prostate tumor–associated marker.
Cytomorphology of Circulating Colorectal Tumor Cells:A Small Case Series
TLDR
This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.
Surgical Removal of Primary Tumor Reverses Tumor-Induced Immunosuppression Despite the Presence of Metastatic Disease
TLDR
The presence of primary tumor suppresses T-cell and antibody responses; however, surgical removal ofPrimary tumor restores immunocompetence even when disseminated metastatic disease is present.
Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood.
TLDR
The data offer a possible explanation for the antivascular effects of cytotoxic agents and suggest potential strategies for targeting the tumor vasculature.
Genes that mediate breast cancer metastasis to the brain
TLDR
It is shown that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization.
...
...