Clemmensen Stine N, Glenthøj Anders J, Heebøll Sara, Nielsen Hans Jørgen, Koch Claus, Borregaard Niels
The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, Copenhagen, Denmark.
Department of Pathology, National University Hospital, Copenhagen, Denmark.
J Cell Mol Med. 2015 Dec;19(12):2865-73. doi: 10.1111/jcmm.12679. Epub 2015 Sep 28.
Olfactomedin 4 (OLFM4) is a secreted glycoprotein predominantly expressed in bone marrow and gastrointestinal tissues. Aberrant expression of OLFM4 has been shown in several cancers. However, the clinical significance hereof is currently controversial. OLFM4 has been proposed as a candidate biomarker of gastrointestinal cancers. To address this, we developed monoclonal antibodies against synthetic peptides representing various segments of OLFM4. We examined expression of OLFM4 in epithelial cells by immunohistochemistry and found that OLFM4 is highly expressed in proliferating benign epithelial cells and in some carcinoma cells. We developed an Enzyme Linked Immunosorbent Assay for OLFM4 and investigated whether plasma levels of OLFM4 reflect colorectal malignancies, but were unable to see any such association. Instead, we observed two populations of individuals with respect to OLFM4 levels in plasma, the majority with OLFM4 in plasma between 0 and 0.1 μg/ml, mean 0.028 μg/ml while 10% of both normals and patients with cancers had OLFM4 between 4 and 60 μg/ml, mean 15 μg/ml. The levels were constant over time. The background for this high plasma level is not known, but must be taken into account if OLFM4 is used as biomarker for GI cancers.
嗅觉介质蛋白4（OLFM4）是一种主要在骨髓和胃肠道组织中表达的分泌型糖蛋白。OLFM4在多种癌症中已显示出异常表达。然而，其临床意义目前存在争议。OLFM4已被提议作为胃肠道癌症的候选生物标志物。为解决这一问题，我们针对代表OLFM4不同片段的合成肽开发了单克隆抗体。我们通过免疫组织化学检测了OLFM4在上皮细胞中的表达，发现OLFM4在增殖的良性上皮细胞和一些癌细胞中高度表达。我们开发了一种针对OLFM4的酶联免疫吸附测定法，并研究了OLFM4的血浆水平是否反映结直肠癌，但未发现任何此类关联。相反，我们观察到血浆中OLFM4水平存在两类人群，大多数人的血浆OLFM4水平在0至0.1μg/ml之间，平均为0.028μg/ml，而正常人和癌症患者中各有10%的人的OLFM4水平在4至60μg/ml之间，平均为15μg/ml。这些水平随时间保持恒定。这种高血浆水平的原因尚不清楚，但如果将OLFM4用作胃肠道癌症的生物标志物，必须予以考虑。
