Which came first, tumor cells or macrophages?

Organ specific metastasis might be based on the specific interactions between chemokines expressed in premetastatic sites and their receptors on tumor cells. The ligand/receptor system in host defense mechanism pertinent to immune cells like macrophages is supposed to be hijacked by tumor cells. Ectopic expression of receptors in tumor cells enables bidirectional signaling between primary tumors and distant metastatic organs. VEGF and TNFalpha secreted from primary tumors signal through circulatory system to stimulate lung endothelial cells and macrophages to enhance production of S100A8 and A9 as well as MIP-1alpha, which in turn stimulate primary tumor cells as well as macrophages in bone marrow to migrate over to the lungs presumably via local chemokine gradient. Although it is beyond discussion to determine which came first, tumor cells or macrophages, the bidirectional signals could amplify the migration of both cells to accomplish metastasis.