TY - JOUR
T1 - Rapid characterization of candidate biomarkers for pancreatic cancer using cell microarrays (CMAs)
AU - Kim, Min Sik
AU - Kuppireddy, Sarada V.
AU - Sakamuri, Sruthi
AU - Singal, Mukul
AU - Getnet, Derese
AU - Harsha, H. C.
AU - Goel, Renu
AU - Balakrishnan, Lavanya
AU - Jacob, Harrys K.C.
AU - Kashyap, Manoj K.
AU - Tankala, Shantal G.
AU - Maitra, Anirban
AU - Iacobuzio-Donahue, Christine A.
AU - Jaffee, Elizabeth
AU - Goggins, Michael G.
AU - Velculescu, Victor E.
AU - Hruban, Ralph H.
AU - Pandey, Akhilesh
PY - 2012/11/2
Y1 - 2012/11/2
N2 - Tissue microarrays have become a valuable tool for high-throughput analysis using immunohistochemical labeling. However, the large majority of biochemical studies are carried out in cell lines to further characterize candidate biomarkers or therapeutic targets with subsequent studies in animals or using primary tissues. Thus, cell line-based microarrays could be a useful screening tool in some situations. Here, we constructed a cell microarray (CMA) containing a panel of 40 pancreatic cancer cell lines available from American Type Culture Collection in addition to those locally available at Johns Hopkins. As proof of principle, we performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep-CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer CMA. In addition, selected molecules that have been previously shown to be differentially expressed in pancreatic cancer in the literature were validated. For example, we observed strong labeling of CA19-9 antigen, a prognostic and predictive marker for pancreatic cancer. We also carried out a bioinformatics analysis of a literature curated catalog of pancreatic cancer biomarkers developed previously by our group and identified two candidate biomarkers, HLA class I and transmembrane protease, serine 4 (TMPRSS4), and examined their expression in the cell lines represented on the pancreatic cancer CMAs. Our results demonstrate the utility of CMAs as a useful resource for rapid screening of molecules of interest and suggest that CMAs can become a universal standard platform in cancer research.
AB - Tissue microarrays have become a valuable tool for high-throughput analysis using immunohistochemical labeling. However, the large majority of biochemical studies are carried out in cell lines to further characterize candidate biomarkers or therapeutic targets with subsequent studies in animals or using primary tissues. Thus, cell line-based microarrays could be a useful screening tool in some situations. Here, we constructed a cell microarray (CMA) containing a panel of 40 pancreatic cancer cell lines available from American Type Culture Collection in addition to those locally available at Johns Hopkins. As proof of principle, we performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep-CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer CMA. In addition, selected molecules that have been previously shown to be differentially expressed in pancreatic cancer in the literature were validated. For example, we observed strong labeling of CA19-9 antigen, a prognostic and predictive marker for pancreatic cancer. We also carried out a bioinformatics analysis of a literature curated catalog of pancreatic cancer biomarkers developed previously by our group and identified two candidate biomarkers, HLA class I and transmembrane protease, serine 4 (TMPRSS4), and examined their expression in the cell lines represented on the pancreatic cancer CMAs. Our results demonstrate the utility of CMAs as a useful resource for rapid screening of molecules of interest and suggest that CMAs can become a universal standard platform in cancer research.
KW - biomarkers
KW - immunocytochemistry
KW - immunohistochemistry
KW - microarrays
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U2 - 10.1021/pr300483r
DO - 10.1021/pr300483r
M3 - Article
C2 - 22985314
AN - SCOPUS:84868317385
SN - 1535-3893
VL - 11
SP - 5556
EP - 5563
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 11
ER -