Tumor cells commence to disseminate early in oncogenesis and are accountable for secondary tumor formation

Abstract

Whereas in cancer the solely primary tumor can often be conquered with therapy, the presence of metastases is frequently lethal. The multi-step process of metastasis starts with tumor cells disseminating from the primary lesion. The most commonly accepted theory states that dissemination starts late in tumorigenesis, when the primary tumor cells have acquired full malignancy. However evidence obtained from mainly breast cancer patients and mouse models, indicates dissemination already starts during early tumor stages, when tumors are still marked as benign. Although tumor dissemination might commence during an early tumor stage, dissemination is only the first step in metastasis. The last step, colonization of a cancer cell at a distant site leading to the outgrowth of secondary tumors, is only completed by a small number of cells. Other evidence indicates that early spreading tumor cells can also fulfill this ultimate step of metastasis. Nevertheless, the spread of cancer cells is often not directly followed by the formation of malignant metastases. One concept that explains this observation is the occurrence of dormancy. Here, tumor cells are kept innocuous by the influence of antiangiogenic factors, the tissue microenvironment they try to settle in, and/or the immune system. This might offer an interesting concept for therapy: if tumor cells cannot be completely eliminated from the body, inducing and prolonging an inactive state might be an option.