Ine 2014, 6:12 http://genomemedicine.com/content/6/2/Page 9 ofcarcinom…

Ine 2014, 6:12 http://genomemedicine.com/content/6/2/Page 9 ofcarcinoma stroma was then found to be associated with advanced clinical stage [86]. In another study, expression of galectin-1 (Gal-1) in the tumor microenvironment (near non-tumor tissues) was associated with poor survival in classic Hodgkin lymphoma (cHL) patients [87]. Tissue interstitial fluid (TIF) from tumors also represents a potential source for circulating biomarkers. TIF from renal cell carcinoma and adjacent normal kidneys was compared by MS, and 138 differentially regulated proteins were identified. Enolase 2 and thrombospondin-1 were found to be upregulated in the sera of renal cell carcinoma patients [88]. Proteomic analysis of sera from mice implanted with orthotopic human oral squamous cell carcinomas allowed discrimination between host- and tumor-derived proteins. Furthermore, 31 murine proteins were identified as differentially regulated, including -2-HS-glycoprotein, complement C3 and C4 and hemopexin [89]. Circulating proteolytic peptides cleaved by carboxypeptidase N in the tumor microenvironment have been shown to have potential for early detection of breast cancer [90]. Integrated analysis of tumor cell line secretome and plasma has provided a means for identifying potential circulating markers. A study that targeted glycoproteins secreted from the human colon carcinoma cell line LIM1215 as a source of potential colorectal carcinoma biomarkers identified a set of glycoproteins that were also found in tumor xenograft TIF and in plasma derived from mice bearing the LIM1215 xenograft tumor [91]. Although host- and microenvironment-derived proteins may well serve as cancer biomarkers, there is a considerable challenge in confirming their specificity for particular tumor types or stages of tumor development, and more broadly their cancer specificity. On the other hand, studies to date suggest that detecting signatures in plasma derived Gemcitabine (hydrochloride) from the tumor microenvironment might provide the necessary sensitivity to determine the presence of tumors at an early stage. Thus, there is likely to be a trade-off between sensitivity and specificity in the use of microenvironment-derived markers for the early detection of tumors.Proteomic analysis in particular has enhanced understanding of how tumor cells PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10389946 modify their microenvironment through production of ECM structural proteins, ECM-modifying proteins and proteases. Proteomics has further enhanced the global identification of protease targets. Combining MS or antibody arrays with experimental approaches, such as co-culture of cancer cells with tumor-associated fibroblasts, has also facilitated the identification of growth and signaling factors produced by stromal and infiltrating cells. Early use of proteomics in cancer research primarily focused on the identification or quantification of proteins, and provided only modest insight into the biological relevance of the findings. As proteomic technologies become more widely utilized, targeted approaches should be applied to elucidate the function of particular proteins. Likewise, as MS technology improves through increased scanning speeds and more sensitive instruments, a larger number of identified proteins and smaller perturbations of protein abundance, along with post-translational modifications, will be observed, allowing for a more fully informative readout of protein expression. Moreover, given that a large fraction of the proteome has an enzymatic function, assessme.