Do inflammatory pathways drive melanomagenesis?
Do inflammatory pathways drive melanomagenesis?
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DOI：
10.1111/exd.12502
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Grichnik, James M.
中科院分区：
文献类型：
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作者：
Schneider, Samantha L.;Ross, Andrew L.;Grichnik, James M.
炎症通路保护宿主，促进组织愈合/修复；然而，过度激活或失调可能是病理性的，具有意想不到的后果，包括恶性进展。炎症和癌症之间的相关性已经得到了很好的证实，抗炎药物已被证明对某些恶性肿瘤具有化学预防作用。现在有数据表明，炎症途径可能在黑色素瘤形成中起关键作用。atp调节的膜通道/受体P2X7和PANX1直接参与黑色素瘤的生长。在其他潜在影响中，P2X7/PANX1通道的打开导致NALP3炎性体的激活，这反过来导致caspase-1激活和激活IL-1水平的增加。caspase-1和IL-1水平的升高与黑色素瘤的进展有关，炎症小体、caspase和IL-1活性的抑制剂都被证明可以抑制黑色素瘤的生长。在许多其他潜在的作用中，IL-1增加环氧化酶-2的表达，导致局部炎症介质如前列腺素E2 （PGE2）的增加。针对这一通路末端的抗炎药物对某些癌症有积极的效果，但总体上对黑色素瘤的疗效仍不明朗。更好地了解途径和适当的干预点可能有助于指导未来的治疗。从这个角度来看，我们将回顾数据并尝试建立一个可能对黑色素瘤形成至关重要的炎症途径，并提出未来的探索方向。
Inflammatory pathways serve to protect the host and promote tissue healing/repair; however, over-activation or dysregulation can be pathological with unintended consequences including malignant progression. A correlation between inflammation and cancer has been well established, and anti-inflammatory medications have been shown to be chemopreventive in certain malignancies. Data are now becoming available that outline an inflammatory pathway that may have a critical role in melanomagenesis. ATP-regulated membrane channels/receptors P2X7 and PANX1 have been directly implicated in melanoma tumor growth. Among other potential effects, opening of the P2X7/PANX1 channel results in activation of the NALP3 inflammasome, which in turn leads to caspase-1 activation and increased levels of activated IL-1. Elevated levels of caspase-1 and IL-1 have been correlated with melanoma progression, and inhibitors of the inflammasome, caspase and IL-1 activity have all been shown to inhibit melanoma growth. Among many other potential actions, IL-1 increases cyclooxygenase-2 expression leading to local increases in inflammatory mediators such as prostaglandin E2 (PGE2). Anti-inflammatory medications targeting the end of this pathway have had positive results for certain cancers but overall remain mixed for melanoma. A better understanding of the pathways and appropriate intervention points may help direct future therapies. In this viewpoint, we will review data and attempt to model an inflammatory pathway that may be critical for melanomagenesis and propose future directions for exploration.