Size Matters: Metastatic cluster size and stromal recruitment in the establishment of successful prostate cancer to bone metastases
This is the title of our latest pre-print that, while submitted to a special issue of BMB edited by Philip Maini and Sandy Anderson, can also be found on biRXiv too. We used the agent-based model we described here and here to do something different this time. Exploring the early stages of metastasis in the bone is very hard using animal models or clinical data. During those early stages, the metastases are too small to be detectable and thus subjected to analyses. Mathematical models do not have these constraints so we decided to use it and see what happens when prostate tumor cells extravasate and try to colonize the bone ecosystem.
The figure embedded in the post shows how certain key aspects of prostate cancer to bone metastases change when we imagine clusters of metastatic cells of different sizes. For each case (1, 10, 100, 250, 500 and 750) we show the impact on the number of tumor cells and on the amount of bone at two different timepoints: early (day 125) and late (day 250). You can see that some of the circles are bigger than others: that reflects the variability of the results. More interestingly, the fraction at the top-right corner in each plot shows how many of the simulations led to the establishment of a successful metastasis (as opposed to one in which the seeding tumor cells do not grow).
These results show that, while seeding a handful of prostate cancer cells in the bone is better than seeding one, the rule the more the merrier is not always true. Having more seeding cells can help the metastasis as the tumor cells together can produce enough disruption in the process of bone homeostasis. Beyond a threshold the more cells the more competition for the limited resources that need to be shared not only between the tumor cells but also between the stromal cells that are co-opted by the metastasis to support the growth.
Let us know what you think if you read the pre-preprint.