Plasma Membrane Proteomics and Its Application in Clinical Cancer Biomarker Discovery

Abstract

Plasma membrane proteins that are exposed on the cell surface have important biological functions, such as signaling into and out of the cells, ion transport, and cell-cell and cell-matrix interactions. The expression level of many of the plasma membrane proteins involved in these key functions is altered on cancer cells, and these proteins may also be subject to post-translational modification, such as altered phosphorylation and glycosylation. Additional protein alterations on cancer cells confer metastatic capacities, and some of these cell surface proteins have already been successfully targeted by protein drugs, such as human antibodies, that have enhanced survival of several groups of cancer patients. The combination of novel analytical approaches and subcellular fractionation procedures has made it possible to study the plasma membrane proteome in more detail, which will elucidate cancer biology, particularly metastasis, and guide future development of novel drug targets. The technical advances in plasma membrane proteomics and the consequent biological revelations will be discussed herein. Many of the advances have been made using cancer cell lines, but because the main goal of this research is to improve individualized treatment and increase cancer patient survival, further development is crucial to direct analysis of clinically relevant patient samples. These efforts include optimized specimen handling and preparation as well as improved proteomics platforms.

Studying Interrelation of PDLIM4 with the Model of CD74-Mediated Development of Breast Cancer

“…CD74 is a γ-subunit of the Main II class Histocompatibility Complex (MHC), hyper expression of which is often observed in malignant tumors of epithelial and mesenchymal nature (Borghese and Clanchy, 2011;Otterstrom et al, 2014). The increased expression of CD74 is associated with active metastasis and negative forecast of breast tumors development (Leth-Larsen et al, 2010;Greenwood et al, 2012;Tian et al, 2012). The previous data about studying correlation of violation of PDLIM4 expression in cells of the tumors that belong to various subtypes of BC indicates that hyperexpression of PDLIM4 is most characteristic for cells of claudindeficient subtype of the triple negative BC type (Kravchenko et al, 2015).…”

Cancer: A proteomic disease

“…These results indicate that multiple subcellular locations exist for proteins in processes related to breast cancer. Leth-Larsen et al [10,11] identified 13 membrane proteins that were over-expressed and three that were under-expressed in a metastatic versus non-metastatic cell line from a total of 1919 protein entries. High ecto-5′-nucleotidase and integrin β1 expression correlated with tumor spread or distant recurrence, and poor outcome within a 10-year follow-up [10].…”

Coagulation Factor and Theranostics: A New Paradigm in Molecular Imaging

“…Comprehensive profiling of the cell surface proteome provides an effective approach for the identification of commonly occurring proteins as well as proteins with restricted expression patterns in cancer (4). Monoclonal antibodies, monoclonal antibody fragments, and drug-loaded delivery systems conjugated with targeting moieties-that is, ligand-are now being used successfully for the targeting of tumors (5).…”