A new target for squamous cell skin cancer?
A new target for squamous cell skin cancer?
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DOI：
10.1111/exd.12576
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Garza, Luis A.
中科院分区：
文献类型：
--
作者：
Kim, Dongwon;Garza, Luis A.
Prostaglandins (PGs) derived from arachidonic acid of cell membrane are synthesized by PG G/H synthase (cyclooxygenase; COX-1/-2) and signal as autocrine/paracrine lipids (1, 2). Similar to other tissues, COX-1 is constitutively expressed in keratinocytes of normal epidermis, whereas COX-2 expression is more variable and regulated (3, 4). COX-2 is induced for example by cytokines and growth factors; accumulated prostaglandins from COX-2 regulate pain, inflammation, and cancers (2, 3). In the case of cancer, increased levels of PGs disrupt differentiation and thus contribute to the sensitization of cells to carcinogens and ensuing hyperplasia (5, 6). Therefore, the inhibition of COX-2 activity with aspirin like compounds has been suggested as a potent chemo-preventive therapy to suppress tumor development, not just in skin but particularly for gastrointestinal cancers (2, 7).While in most cases COX-2 appears to support oncogenesis, opposite evidence that constitutive expression of COX-2 prevents the development of skin tumor has been reported suggesting that distinct downstream PGs mediated by COX-2 in vivo might have opposing effects and thus explain these variable results (8). This is quite classic for this pathway; despite the plethora of physiologic systems were COX-2 appears active, aspirin has a very limited side effect profile. This is likely because in most cases of inhibition of COX-2, the simultaneous inhibition of both positive and negative individual downstream prostaglandin players has a net zero physiologic effect. The most classic opposing prostaglandins are PGE2 and PGD2. PGE2 has been shown to correlate with the oncogenic effects of COX-2, but less work has been done on PGD2. To better understand the functions of PGD2 and its metabolites in skin tumors, Mantel et al. evaluated the role of Aldo-keto reductase 1C3 (AKR1C3) expression in proliferation of SCC cell lines.
