Proteomic profiling of the tumor microenvironment: recent insights and the search for biomarkers

Table 1 Highlights from proteomic studies of the tumor microenvironment

	Experimental system	Approach	Key proteins
Tumor ECM	EMT in murine cancer cells [24]	MS of subcellular fractions	Fibronectin, collagens, laminins
	Metastatic melanoma cells [26]	Secretome MS	Fibronectin, ECM1, SPARC, osteopontin
	Hepatocarcinogenesis [29]	ECM MS	Collagen splice variants, nidogen, decorin, perlecan
	Cell attachment to collagen [34]	Phosphoprotein analysis	DBF4, GRK6, PAK2, FAK/ PTK2
	Breast cancer metastasis [34]	MS	Cystatin-M
	Tumor invasiveness [41]	Antibody libraries	hsp90α
Tumor-stroma interactions	Tumor versus normal stroma [45]	Laser capture + MS	CapG (actin-regulating protein)
	CAFs [49]	MS of cell lysates	Caveolin-1
	MMP7 effect of CAFs [50]	MS of cell lysates	IGFBP5
	Lung cancer TME [54]	Cytokine assays	CXCL1, IL-18
	Stromal cell secretome [60]	Antibody arrays	HGF
Immune cells in the tumor microenvironment	Mesothelioma effusions [67]	Antibody arrays	HGF, MIP-1d, MIP-3a, NAP-2
	Ovarian tumor macrophages [68]	MS of supernatants	14-3-3 zeta
	CD45RA + versus CD45RO + T cells [70]	MS of cell lysates	Cell redox proteins
	MDSCs + IL1B [72]	MS of cell lysates	FAS pathway and caspase network

Some studies have focused on the ECM, others on tumor-stroma interactions and on immune cells infiltrating the tumor microenvironment. These studies have utilized various experimental systems applied to different tumor types. Some of the key proteins that have been found to be involved are highlighted, illustrating the numerous protein families that play a role in the tumor microenvironment. Abbreviations: CXCL1, interferon-inducible protein-1; DBF4, activator of S-phase kinase 4; GRK6, G-protein coupled receptor kinase 6; FAK, focal adhesion kinase; hsp90α, heat shock protein 90α; IGFBP5, insulin growth factor binding protein 5; IL-18, interleukin-18; IL1B, interleukin1B; MIP-1d, macrophage inflammatory protein-1d; MIP-3a, macrophage inflammatory protein-3a; MMP7, matrix metalloproteinase 7; NAP-2, neutrophil-activating peptide-2; PAK2, SPARC, secreted protein, acidic, cysteine rich; TME, tumor microenvironment.

ISSN: 1756-994X