Transfer of malignant traits as opposed to migration of cells: A novel concept to explain metastatic disease

Abstract

Metastatic disease is believed to develop following dissemination of cells to target organs. Inability of this theory to effectively explain certain phenomena such as patterns of metastatic spread, late metastasis formation, different gene patterns between primary cancer and metastasis have brought forward the need for alternative models. Recent discoveries have strengthened the validity of theories supporting a humoral transfer of malignant traits as opposed to migration of malignant cells to explain metastatic disease in cancer patients. In light of this new evidence, we would like to highlight a model that offers a new perspective to explain cancer metastasis. In the system that we theorize, genetic material released by cancer cells would travel, either free or packed in exosomes, through the blood. Target cells located in organs deriving from the same embryological layer might uptake this genetic material due to expression of specific receptors. Interplay with the immune system would determine the fate of these oncofactors and would regulate their ability to circulate in the blood, integrate in the genome and be transcribed. We also hypothesize that the expression of cell membrane receptors such as integrins, to which cancer exosomes ligate might be mediated by inherited or acquired oncosuppressor mutations.