3 Recent research has shown that ligands to serpentine receptors play an important role in the regulation of tumor cell migration. 2 On the other hand, the comparative gene expression profiling of primary breast tumors and distant metastases showed striking similarity, suggesting that the metastatic capability in breast cancer is an inherent feature and is not based on clonal selection. mutations of the tumor-suppressor gene MADH4, occur more frequently in metastatic tumors. 1 Their theory is supported by the finding that certain mutations, e.g. On one hand, Bernards and Weinberg propose that mutant genes confer a Darwinian selective advantage for a clonal selection of metastatic tumor cells. In the postgenomic era of cancer research, there is an intensive discussion to what extent the development of metastases is genetically based, and what role can be ascribed to environmental factors. Thus, our work contributes to the understanding of the basic cellular mechanisms of metastasis development, and furthermore delivers a rationale for the chemopreventive use of clinically established β-blockers for the inhibition of metastases. Additionally, experiments using human tissue microarrays showed that 70–90 percent of breast, colon, and prostate carcinoma tissues express the relevant β2-adrenoceptor. However, the growth of the primary tumor was not affected by either treatment. The development of lumbar lymph node metastases in athymic BALB/c nude mice increased with the application of norepinephrine via microosmotic pumps, while propranolol inhibited this effect. We now provide for the first time evidence for the in vivo relevance of this neurotransmitter-driven regulation using PC-3 prostate carcinoma cells.
We have shown previously that the migration of breast, prostate, and colon carcinoma cells is enhanced by the stress-related neurotransmitter norepinephrine in vitro, and that this effect can be inhibited by the β-blocker propranolol.
Tumor cell migration, a prerequisite for metastasis development, is not merely genetically determined, but is distinctly regulated by signal substances of the environment including chemokines and neurotransmitters. The detection of metastases in cancer patients is correlated with a poor prognosis, and over 90% of all deaths from cancer are not due to the primary tumor, which often can be successfully treated, but are due to the metastases. The development of metastases is a decisive step in the course of a cancer disease.