The Tumor Microenvironment: Key to Early Detection

Abstract

The tumor microenvironment plays an important role equal to the tumor cell population in the progression of cancer. Consisting of stromal fibroblasts, inflammatory cells, components of the vasculature, normal epithelia, and extracellular matrix, the surrounding environment interacts or "cross-talks" with tumor cells through the release of growth factors, cytokines, proteases, and other bioactive molecules. Tumor growth, formation of new vascular networks, evasion of the host immune system, and invasion and metastasis are processes that co-evolve and become finely optimized and regulated within the tumor microenvironment. However, relatively recent reports on three areas of study have come together to add new levels of complexity to the tumor microenvironment. These include ectodomain shedding of proteins, shedding of membrane-derived vesicles, and novel roles for phospholipids. These dynamic changes that take place in the tumor microenvironment provide new avenues for study and for the early detection of cancer, whereas proteomic technologies provide the means to detect these unique proteins and lipids. Here we review the evolving concepts of the tumor microenvironment that, together with advances in proteomic technologies, hold the promise to facilitate the detection of early-stage cancer.

Discovery and Verification of Head-and-neck Cancer Biomarkers by Differential Protein Expression Analysis Using iTRAQ Labeling, Multidimensional Liquid Chromatography, and Tandem Mass Spectrometry

“…Furthermore YWHAZ has also been reported to be overexpressed in stomach cancer (27) and in breast and prostate tumor model systems (28,29). More importantly, YWHAZ is not overexpressed in endometrial and lung cancer tissue samples (18,30), thus illustrating the fact that this protein can provide some selectivity in discriminating among different cancer types.…”

“…blood, as every tissue or organ can potentially discharge into blood. Furthermore the tumor microenvironment plays an important role in cancer progression (18), and the examination of protein expression in tissues from a homogenate of different cell types takes into account the contributions of the tumor microenvironment.…”

Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

“…Growth factors and cytokines, serine proteases, matrix metalloproteinases (MMPs), cellular adhesion molecules, tumor cell stromal interactions, and phospholipids are actively involved in the regulation of these processes [8][9][10]. Thus, understanding the tumor microenvironment and its regulatory mechanism is critical for the development of effective therapies to treat metastatic endometrial carcinoma.…”

Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

“…Autocrine and paracrine signaling mechanisms mediate the interactions of growth and differentiation factors with their receptors, which drive normal development and a variety of developmental diseases such as cancers (Ariztia et al, 2006). Whereas the nature of the ligand defines the interaction with its cognate receptor and the receptor-initiated signaling mechanisms, the mode of ligand presentation is also a major determinant of receptor activation and has a major role in the biological responses.…”