Conflicting Biomedical Assumptions for Mathematical Modeling: The Case of Cancer Metastasis
The tumor's development starts with its growth at the primary location (primary tumor). In metastatic progression, some cells from the primary tumor detach from the colony (detachment), enter blood or lymph vessels (intravasation) and travel within the body (migration/transport). Next, the traveling cells exit blood or lymph vessels (extravasation) and colonize new sites in the body. There, they divide and form tiny colonies at first (micrometastasis), followed by further cell proliferation, recruitment of blood vessels (angiogenesis) that provide small colonies with sufficient nutrients to develop into large tumors (macrometastasis). It is currently unclear if secondary colonies can re-metastasize to form tertiary and quaternary colonies (dotted line indicating a cyclic process).