Mareel M, Madani I
Department of Radiotherapy and Experimental Cancer, University Hospital Gent, Belgium.
Acta Chir Belg. 2006 Nov-Dec;106(6):635-40. doi: 10.1080/00015458.2006.11679971.
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.
有着百年历史的“种子”与“土壤”理论解释了癌症转移的关键特征：早期起始；晚期出现；器官特异性。“种子”即癌细胞；它会发生基因改变，扰乱维持正常组织结构的细胞活动，从而启动侵袭性和转移性肿瘤的形成。“土壤”由肿瘤相关宿主细胞组成：内皮细胞和周细胞形成血管和淋巴管，被血管内皮生长因子（VEGF）吸引至癌细胞；神经细胞；成纤维细胞被癌细胞释放的转化生长因子（TGF）-β转化为肌成纤维细胞；炎症细胞，被癌症趋化因子吸引；破骨细胞被骨髓中的转移性癌细胞激活。所有这些宿主细胞都与癌细胞持续进行分子间的相互作用，影响侵袭和转移。肿瘤相关宿主细胞本身具有侵袭性，其中一些在癌细胞之前到达转移部位。肿瘤相关宿主细胞的高放射敏感性使我们推测放疗可能会影响侵袭和转移。电离辐射对骨转移的镇痛作用以及预防肺癌脑转移可能归因于宿主细胞的改变。我们建议在制定癌症放疗、化疗和手术的新策略时考虑肿瘤相关宿主细胞。
