The emergence of tumor metastases.

The appearance of metastases is an ominous sign in the natural history of any malignant tumor. Their presence implies a high tumor burden and greatly decreases the probability of a cure. Metastasis development requires the evolution of tumor cells that can survive in an environment that is normally not supportive to their growth and such cells must leave the tumor to establish tumor niches elsewhere. The interactions between the appearance of cells with metastatic ability in the primary tumor and their exit from the tumor lead to complex dynamics that can be either beneficial or detrimental to the tumor. We develop a simple mathematical model to illustrate how the interplay between mutation rate and export probability affects the intratumoral dynamics of metastasis-enabled cells and the rate of metastases formation.