Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

We have evidence for the existence of a structure called tumor microenvironment of metastasis or TMEM, which is composed by a proangiogenic macrophage a, a Mena overexpressing tumor cell and an endothelial cell where the three cell complex is in direct contact with a blood vessel wall. We detected primary tumor TMEM P-TMEM in pre-malignant lesions. The P-TMEM is required to support early dissemination of pre- malignant neoplastic cells early DTCs. We further hypothesize that after extravasation at secondary site TMEM STMEM,in order to exit dormancy a stable S-TMEM structure needs to be maintained and that early DTCs cannot sustain its assembly possibly because they lack a persistent proangiogenic M recruiting program. Our rationale is that by understanding early dissemination and dormancy of DTCs we will find ways to eradicate dormant DTCs and prevent metastasis.