  Resection of primary tumors is often followed by accelerated growth of
metastases. Here we propose that this effect may be due to the fact that
resection of primary tumor results in a decrease in the total systemic amount
of angiogenesis stimulators, such as VEGF and bFGF. This in turn causes
decrease in the systemic level of angiogenesis inhibitors, such as PF-4 and
TSP-1, which at least temporarily relieves inhibition of secondary tumors,
allowing them to grow. This construct is predicated on the notion that systemic
level of angiogenesis inhibitors is regulated by the systemic level of
angiogenesis stimulators, as the host is trying to maintain the homeostatic
balance of stimulators to inhibitors in the body. We evaluate this hypothesis
using a conceptual mathematical model and show that indeed, this mechanism can
explain accelerated growth of secondary tumors following resection of a primary
tumor. We also show that there exists a tradeoff between time of surgery and
time to onset of metastatic growth. We conclude with a discussion of possible
therapeutic approaches that may counteract this effect and reduce metastatic
recurrences after surgery.
