An outsider's perspective—ecotaxis revisited: an integrative review of cancer environment, iron and immune system cells

Abstract

Lymphoid cell and tumor cell migration share similarities: 1. migration to specific microenvironments; 2. increased microvasculature with increased growth; 3. cell division. At the same time, contrasting aspects between the two merit attention: 1. failure of tumors to return to microvasculature quiescence; 2. failure of malignant cells to stop dividing; 3. failure of tumor cells to re-enter the circulation after returning to a non-activated phenotype. Analysis of these contrasting aspects leads to the reviewing of unexpected roles of immune cells in the tumor environment, recent work on ferroportin expression with lack of iron export by tumor cells, iron export by M2 macrophages, and deficient dendritic cells (DCs) in the tumor environment. DCs in lymph nodes have recently been found to bring lymph node vasculature to quiescence after antigen stimulation. Contrary to current dogma, the evidence is that some immune system cells in the tumor environment may be favoring regulators instead of diminishing tumor growth. In addition, recent data herein reviewed will make it difficult not to consider iron and iron gene expression as relevant components of the tumor environment. Finally, I conclude with wondering how much longer what I call the ‘Hunter Paradigm’ will dominate cancer research and immunology and how timely it is to acknowledge in the first decade of a new century, Mina Bissell as a pioneer in the change of that paradigm in Cancer Research.

“Suppose he'd listened to the erudite committee; He would have only found where not to look”

WH Auden