Tumour-associated host cells participating at invasion and metastasis : targets for therapy?

The 100-year old "seed" and "soil" theory explains key features of cancer metastasis: early initiation; late appearance; organ-specificity. The seed is the cancer cell; it undergoes genetic alterations, disturbing the cellular activities that maintain normal tissue organisation and, so, initiating the formation of invasive and metastatic tumours. The soil consists of tumour-associated host cells: endothelial cells and pericytes forming blood-and lymph vessels attracted to the cancer cells by vascular endothelial growth factor (VEGF); nerve cells; fibroblasts converted into myofibroblasts by cancer cell-released transforming growth factor (TGF)-beta; inflammatory cells, attracted by cancer chemokines; osteoclasts activated by metastatic cancer cells in the bone marrow. All these host cells engage in continuous molecular cross talk with the cancer cells, influencing invasion and metastasis. Tumor-associated host cells are themselves invasive and some of them arrive at the site of metastasis ahead of the cancer cells. The high radiosensitivity of the tumor-associated host cells lead us to speculate that radiotherapy may affect invasion and metastasis. Analgesic effects on bone metastasis and prevention of lung metastasis to the brain by ionizing radiation are possibly due to alterations of host cells. We suggest to consider tumour-associated host cells when developping new strategies for cancer radiotherapy, chemotherapy and surgery.