The "inherent vice" in the anti-angiogenic theory may cause the highly metastatic cancer to spread more aggressively.
The "inherent vice" in the anti-angiogenic theory may cause the highly metastatic cancer to spread more aggressively.
复制标题
抗血管生成理论中的“固有缺陷”可能会导致高度转移的癌症更积极地扩散
DOI：
10.1038/s41598-017-02534-1
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发表时间：
2017-05-24
影响因子：
4.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Wang D;Tan C;Xiao F;Zou L;Wang L;Wei Y;Yang H;Zhang W
尽管抗血管生成（AA）治疗在临床实践中被广泛使用，但其经常受到疗效不足和内在耐药性的挑战。一些研究报道，AA治疗甚至可以增加肿瘤转移。然而，这究竟是由于特定的AA药物导致特定的肿瘤转移，还是因为抗血管生成理论存在某种“固有的缺陷”，可能不可避免地导致肿瘤扩散，仍然是一个谜。在此，我们设计了一个模型，使用物理屏障完全阻断肿瘤血液供应，以检查肿瘤在这种情况下的行为。令人惊讶的是，我们发现切断血液供应既不能消除原发性肿瘤细胞，也不能阻止局部侵袭或远处转移的形成。通过运用数学方法模拟肿瘤行为，我们发现阻断肿瘤供血可能会导致一个必然的后果：能够耐受血虚的细胞被“自然选择”而存活，而一部分细胞则被持续的环境应激促进逃离“饥饿”区，直至遍布全身。这可能是AA策略的固有缺点，这将不可避免地导致肿瘤，特别是高转移性肿瘤，更积极地扩散。
Although anti-angiogenic (AA) therapy is widely used in clinical practice, it is often challenged by insufficient efficacy and intrinsic resistance. Some studies have reported that AA therapy can even increase tumor metastasis. However, whether this is due to a specific AA drug causing a specific tumor to metastasize or because the anti-angiogenic theory has some “inherent vice” that may inevitably lead to tumor dissemination remains a mystery. Herein, we designed a model that completely blocks tumor blood supply using a physical barrier to examine tumor behavior in such circumstances. Surprisingly, we found that cutting off the blood supply could neither eliminate the primary tumor cells nor prevent local invasion or formation of distant metastases. By using a mathematical method to simulate tumor behavior, we found that blocking tumor blood supply may lead to an inevitable consequence: the cells that can tolerate blood deficiency are “naturally selected” and survive, whereas a portion of cells are promoted to escape from the “starvation” area by the consistent environmental stress until they are spread throughout the body. This may be an intrinsic disadvantage of the AA strategy, which will inevitably cause the tumor, particularly highly metastatic tumors, to spread more aggressively.