  Two models of circulating tumor cell (CTC) dynamics have been proposed to
explain the phenomenon of tumor 'self-seeding', whereby CTCs repopulate the
primary tumor and accelerate growth: Primary Seeding, where cells from a
primary tumor shed into the vasculature and return back to the primary
themselves; and Secondary Seeding, where cells from the primary first
metastasize in a secondary tissue and form microscopic secondary deposits,
which then shed cells into the vasculature returning to the primary. These two
models are difficult to distinguish experimentally, yet the differences between
them is of great importance to both our understanding of the metastatic process
and also for designing methods of intervention. Therefore we developed a
mathematical model to test the relative likelihood of these two phenomena in
the subset of tumours whose shed CTCs first encounter the lung capillary bed,
and show that Secondary Seeding is several orders of magnitude more likely than
Primary seeding. We suggest how this difference could affect tumour evolution,
progression and therapy, and propose several possible methods of experimental
validation.

Tissues and Organs;Populations and Evolution