CRABP2 and FABP5 expression levels in diseased and normal pancreas
CRABP2 and FABP5 expression levels in diseased and normal pancreas
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DOI：
10.1016/j.anndiagpath.2020.151557
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发表时间：
2020-08-01
影响因子：
2
通讯作者：
Kocher, Hemant M.
中科院分区：
文献类型：
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作者：
Hughes, Christine S.;Chinaleong, Jo-Anne;Kocher, Hemant M.
近年来，全反式维甲酸（ATRA）等药物的间质靶向治疗被认为是治疗胰腺导管腺癌（PDAC）的一种有前途的途径。ATRA向核受体的细胞内转运通过脂肪酸结合蛋白5（FABP5）或细胞视黄酸结合蛋白2（CRABP 2）进行，决定下游基因的转录，从而决定最终的细胞表型。在这里，我们探讨了各种胰腺疾病患者胰腺组织中每种蛋白质的水平，（胰腺导管腺癌（PDAC）、慢性胰腺炎（CP）、胆管癌（CC））。我们证明PDAC中活化的成纤维细胞或胰腺星状细胞（PSC）以及其他疾病中CRABP 2和FABP 5的表达显着较低。在CC和CP中，对比静止的成纤维细胞。静止的成纤维细胞一致地显示高FABP 5：CRABP 2比率的模式，而所有非PDAC组织中的PSC显示低FABP 5：CRABP 2比率。PDAC患者中的PSC具有一系列FABP5：CRABP 2比率（高、均匀和低）CRABP 2在癌性上皮细胞（PDAC）中的表达低于正常上皮细胞。这也存在于其他疾病状态（CP，CC）中。与成纤维细胞的模式相比，PDAC上皮细胞中的FABP5表达与正常上皮细胞的FABP5表达相匹配。然而，与PDAC上皮细胞相比，正常上皮细胞具有高的FABP5：CRABP 2比率。这些比值可能与肿瘤进展和总生存期相关。这些发现可以在体外细胞裂解物中得到证实。CRABP 2和FABP5水平和比率可以作为有价值的生物标志物。
Recently, stromal targeting, by agents such as All trans retinoic acid (ATRA), has been regarded as a promising avenue for the treatment of pancreatic ductal adenocarcinoma (PDAC). The intra-cellular transportation of ATRA to the nuclear receptors is performed by either: fatty acid binding protein 5 (FABP5) or cellular retinoic acid binding protein 2 (CRABP2), dictating the transcription of downstream genes and, thus, eventual cell phenotype. Here, we explored the levels of each protein, in pancreatic tissues of patients presenting with a range of pancreatic diseases (pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), cholangiocarcinoma (CC)).We demonstrate that there is a significantly lower CRABP2 and FABP5 expression in activated fibroblasts or pancreatic stellate cells (PSC) in PDAC, as well as other diseased pancreas as in CC and CP, versus quiescent fibroblasts. The quiescent fibroblasts consistently show a pattern of high FABP5:CRABP2 ratio, whereas PSC in all non-PDAC tissues showed a low FABP5:CRABP2 ratio. PSC in PDAC patients had a range of FABP5:CRABP2 ratios (high, even and low).There was a lower CRABP2 expression in cancerous epithelial cells (PDAC) versus normal epithelial cells. This is also present in other disease states (CP, CC). Contrasting to the patterns seen for fibroblasts, the FABP5 expression in PDAC epithelial cells matched that of the normal epithelial cells. However, the normal epithelial cells had a high FABP5:CRABP2 ratio, compared to the PDAC epithelial cells. These ratios may have correlation with tumor progression, and overall survival. These findings could be confirmed in in vitro cell lysates. CRABP2 and FABP5 levels and ratios could serve as valuable biomarkers.