Periostin: a putative mediator involved in tumour resistance to anti-angiogenic therapy?
Periostin: a putative mediator involved in tumour resistance to anti-angiogenic therapy?
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DOI：
10.1042/cbi20110171
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发表时间：
2011-11-01
影响因子：
3.9
通讯作者：
Xu, Ge-Liang
中科院分区：
文献类型：
--
作者：
Wang, Wei;Ma, Jin-Liang;Xu, Ge-Liang
尽管在开发用于癌症治疗的抗血管生成剂方面取得了进展，但癌症患者存活期的增加仍然相当有限。抗血管生成治疗的一个主要障碍是耐药性的出现。了解使肿瘤能够逃避抗血管生成治疗的分子机制对于提高治疗效果是有价值的。靶向血液供应通常会引起肿瘤的缺氧反应，从而引发一系列适应性变化，导致耐药表型。Periostin是一种分泌型细胞外基质蛋白，主要由癌相关成纤维细胞在低氧应激下产生。由于CAF与肿瘤对血管生成阻断的抗性偶然相关，并且骨膜蛋白可以影响肿瘤生物学的许多方面，因此我们假设骨膜蛋白可能是癌症治疗中涉及抗血管生成抗性的关键介质。该假设间接地得到以下事实的支持：（a）高水平的骨膜蛋白促进肿瘤血管生成;（B）骨膜蛋白改善缺氧条件下的癌细胞存活;和（c）骨膜蛋白的遗传调节诱导EMT（上皮-间充质转化）并增强癌细胞侵袭和转移，这代表了抗癌治疗的逃避机制。这一假设的验证将使我们更深入地了解耐药机制，并为改善抗血管生成治疗的疗效提供理论依据。
Despite advances in the development of anti-angiogenic agents for cancer treatment, the increase in the survival duration of cancer patients is still rather modest. One major obstacle in anti-angiogenic therapy is the emergence of drug resistance. Understanding the molecular mechanisms that enable a tumour to evade anti-angiogenic treatment is valuable to improve therapeutic efficacy. Targeting blood supply usually causes hypoxic responses of tumours that trigger a series of adaptive changes leading to a resistant phenotype. Periostin, a secreted ECM (extracellular matrix) protein, is mainly produced by CAFs (cancer-associated fibroblasts) on hypoxic stress. As CAFs have been casually linked to tumour resistance to angiogenesis blockade and periostin can influence many aspects of tumour biology, we hypothesized that periostin might be a crucial mediator involved anti-angiogenic resistance in cancer treatment. This hypothesis is indirectly supported by the following facts: (a) high levels of periostin promote tumour angiogenesis; (b) periostin improves cancer cell survival under hypoxic conditions; and (c) genetic modulation of periostin induces EMT (epithelial-mesenchymal transition) and enhances cancer cell invasion and metastasis, which represents an escape mechanism from anticancer treatment. Testing and confirmation of this hypothesis will give more insight into the resistance mechanisms and provide the rationale for improvement of therapeutic outcome of anti-angiogenic therapy.