Indraccolo Stefano, Favaro Elena, Amadori Alberto
Istituto Oncologico Veneto, Padova, Italy.
Cell Cycle. 2006 Aug;5(16):1751-5. doi: 10.4161/cc.5.16.2985. Epub 2006 Aug 15.
Tumor dormancy, a complex and still poorly understood phenomenon observed both in experimental models and in patients, has been associated with insufficient angiogenic capacity. A defined event, termed "angiogenic switch" and characterized by an imbalance between pro- and anti-angiogenic factors, often marks interruption of the dormant state, thus triggering invasive tumor growth. In our current view, sustained angiogenesis is considered essential in promoting this transition. Recently, we demonstrated that co-administration of proliferation-arrested Kaposi's sarcoma cells or recombinant angiogenic factors interrupts dormancy of poorly angiogenic leukemia cells by providing a brief angiogenic burst. These findings indicate that even a transient angiogenic switch can prime progressive tumor growth and suggest that tumor angiogenesis is a process requiring a higher amount of angiogenic factors for its induction than maintenance. Here we discuss the implications of these observations on our view of tumor angiogenesis and on the therapeutic potential of angiogenesis inhibitors.
肿瘤休眠是一种在实验模型和患者中均有观察到的复杂且仍未被充分理解的现象，它与血管生成能力不足有关。一个特定的事件，称为“血管生成开关”，其特征是促血管生成因子和抗血管生成因子之间的失衡，常常标志着休眠状态的中断，从而触发肿瘤的侵袭性生长。在我们目前的观点中，持续的血管生成被认为是促进这种转变的关键。最近，我们证明，联合给予增殖停滞的卡波西肉瘤细胞或重组血管生成因子，通过提供短暂的血管生成爆发，可中断血管生成能力较差的白血病细胞的休眠。这些发现表明，即使是短暂的血管生成开关也能启动肿瘤的进展性生长，并提示肿瘤血管生成是一个诱导过程比维持过程需要更多血管生成因子的过程。在此，我们讨论这些观察结果对我们关于肿瘤血管生成的观点以及血管生成抑制剂治疗潜力的影响。
