Upregulation of Mrps18a in breast cancer identified by selecting phage antibody libraries on breast tissue sections

Abstract

BackgroundOne of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation.MethodIn this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers. A small subpopulation of breast cells expressing both cytokeratin 19 and cytokeratin 14 was targeted using a novel selection procedure.ResultsWe identified the mitochondrial ribosomal protein s18a (Mrps18a) as a protein which is upregulated in breast cancer. However, Mrps18a was not homogeneously upregulated in all cancer cells, suggesting the existence of sub-populations within the tumor. The upregulation was not confined to cytokeratin 19 and cytokeratin 14 double positive cells.ConclusionThis study illustrates how phage display can be applied towards the discovery of proteins which exhibit changes in their expression patterns. We identified the mitochondrial protein Mrps18a as being upregulated in human breast cancer cells compared to normal breast cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2987-5) contains supplementary material, which is available to authorized users.

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis

“…Recent studies reported that the expression of MRPS18A is upregulated in breast cancer cells compared to normal cells, but it cannot be regarded as a unique biomarker because it was found both in normal and cancer cells. However, the increased expression level in cancer cells is explained by the increased energy metabolism of cancer cells, and it could pave the way for new diagnostic and therapeutic routes to be explored …”

“…However, the increased expression level in cancer cells is explained by the increased energy metabolism of cancer cells, and it could pave the way for new diagnostic and therapeutic routes to be explored. 34 As a secretory protein encoded by the CST1 gene, CST1 which belongs to the type 2 cystatin (CST) superfamily. Studies have implied that cystatins play pivotal roles in tumor invasion and metastasis.…”

Antibody Identification for Antigen Detection in Formalin-Fixed Paraffin-Embedded Tissue Using Phage Display and Naïve Libraries

“…The present section describes antibody selection on whole FFPE sections [ 57 , 58 ], and also three on-slide micro-selection strategies to target specific tissue structures or cell clusters ( Figure 1 ). Two of them rely on the excision of the positive tissue by laser-assisted microdissection [ 59 , 60 , 61 , 62 , 63 ] or with a micropipette [ 64 ]; the third one blocks bacterial replication of irrelevant phages through UV-induced DNA damage [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. All these strategies can be used on FFPE and frozen tissue sections.…”

“…One of the characteristics of the shadow stick method is to “provide few and highly relevant output clones” [ 65 ]. The number of selected clones is low enough to allow their direct screening: eight clones per selection after optimization in 2010 [ 66 ]; 12 clones in three selections in 2013 [ 68 ]; 40 clones in two selections on FFPE sections in 2015 [ 65 ]; 315 clones in 13 selections on frozen sections in 2015 and 2016 [ 69 , 70 ]; and 93 clones in 8 selections on frozen sections in 2017 [ 71 ]. This low clone number greatly facilitates the subsequent screening steps.…”

Clinical implications of phage display technique: Digging deeper in diagnostic and therapeutic grounds.

“…The tumors are known to present a great level of heterogeneity that has challenged an early diagnosis and the treatment of the cancer. Antibodies and peptides against CD271+ [57], Mrps18a [58], neuropilin-1, platelet-derived growth factor and human epidermal growth factor receptor 2 have been identified using this technique [59]. To it, cell biopanning has also been studied in this aspect [60][61][62] 6.5 Colon cancer: Hou, et al [63] reported peptide CBP-DWS, using phage display, that had an ability to bind to colon cancer cells.…”