Fig. 6

Proteomic analysis of low and high mammographic density (MD) tissue. Proteins exhibiting >2-fold difference in abundance between tissue samples derived from patients with low and high MD. Red bars indicate greater abundance in tissue from patients with high MD: apolipoprotein D (APOD), a breast cyst fluid component and potentially a progesterone transporter [65], which is expressed in ductal carcinoma [66]; prolactin-inducible protein (PIP), a fibronectin-degrading aspartyl proteinase [67], which is frequently expressed in androgen receptor-positive breast tumours [68]; polymeric immunoglobulin receptor (PIGR), an epithelial cell-surface-located [69] biomarker of metastatic breast cancer [70]; zinc-alpha-2-glycoprotein (AZGP1), which stimulates lipolysis in adipocytes and is expressed in up 50 % of human breast cancers [71]; collagen XVI alpha 1 chain and periostin (COL16A1 and PSTN), extracellular matrix (ECM)-regulating proteins, which control collagen fibril interactions [50–52]; and two further proteins: immunoglobulin J (IGJ) and ACTN4, which have no known links to cancer or ECM remodelling [72, 73]. Proteins with a greater abundance in low MD tissue include: myeloperoxidase (MPO), serum markers of breast cancer including the neutrophil activity marker myeloperoxidase [74]; S100A8 and S100A9 (proinflammatory regulators [75, 76]), which play an as-yet poorly defined role in metastasis [77, 78]; C5 (a proteolytic degradation product of complement C5 [79], S100A11), which facilitates keratinocyte differentiation; apolipoprotein C-I (APOC1), an inhibitor of lipoprotein/LDL receptor binding [80], which may promote chronic low-grade inflammation and breast cancer [81]; inter-alpha-trypsin inhibitor heavy chain H1 (H1ITIH1), a hyaluronan binding protein [82], which is implicated in inflammation and downregulated in breast cancer [83]; HRG, histidine-rich glycoprotein, which inhibits tumour vascularisation [84, 85]; apolipoprotein A-I (APOA1), which is reported to be protective against breast cancer [86]; SERPINB6, an ECM protease inhibitor [54]; coagulation factor XIII A chain (F13A1), which inhibits degradation of collagen precursors [53]; glucose-6-phosphate isomerase (GPI), which modulates cancer cell phenotype [87]; apolipoprotein A-IV (APOA4) - blood plasma levels are significantly reduced in BRCA1 mutation carriers modulate [88]; laminin subunit beta-2 (LAMB2), a component of basement membranes, which is implicated in tumour angiogenesis [89]. Both serum paraoxonase/arylesterase 1 (PON1) and mitochondrial 60 kDa heat shock protein (HSPD1) appear to be unrelated to either matrix homeostasis or tumourigenesis