Table 3.
Proteins detected by multiplex bead-based flow in EVs in at least 5 of 7 patients
| Protein | Cellular expression | Extra information | Present in number of patients | Reference |
|---|---|---|---|---|
| Proteins detected at high level, MFI > 400 | ||||
| CD9 | Platelets, pre-B-cells, eosinophils, basophils, activated T-cells, endothelial and epithelial cells | EV marker, belonging to the tetraspanin family. It can modulate cell adhesion and migration, and is suggested to have a function in breast cancer metastasis. | 7 | [13, 21] |
| CD29 (Integrin beta 1) | Leukocytes, mesenchymal stem cells, cancer stem cells | Cell adhesion molecule and a marker of cancer stem cells. CD29 expression on EVs has been shown to be increased in breast cancer tissues. | 7 | [18, 24, 55] |
| CD42a | Platelets and megakaryocytes | Platelet marker. Platelets are suggested to be involved in all steps of tumorigenesis including tumor growth, tumor cell extravasation and metastasis. Platelet EVs have been shown to have a pro-coagulant function and be associated with aggressive tumors and poor prognosis. | 7 | [13, 56]. |
| CD44 | Various cells of different origins, e.g. cancer stem cells, hematopoetic cells and cells in the epidermis. | A cell adhesion molecule, receptor for e.g. hyaluronic acid. Highly expressed in many cancers. It has a role in cell migration, tumor growth and progression. It has been detected on EVs derived from plasma from breast cancer patients. | 7 | [14, 19, 25, 26] |
| CD62p (P-selectin) | Activated endothelial cells, platelets and megakaryocytes | Activation marker, expressed on activated endothelial cells and platelets. Associated with a high risk of venous thrombosis in cancer patients. | 5 | [27, 28] |
| CD63 | Activated platelets, monocytes, macrophages, granulocytes, and endothelial cells | EV marker, belonging to the tetraspanin family. | 7 | [13] |
| CD81 | B- and T-cells, NK cells, monocytes, thymocytes, DCs, endothelial cells, and fibroblasts | EV marker, belonging to the tetraspanin family. | 7 | [13] |
| CD105 | Mature endothelial cells, mesenchymal stem cells, erythroid precursors, activated monocytes and macrophages. Plasma levels of soluble CD105 have been shown to correlate with metastasis in patients with breast cancer | Accessory receptor for transforming growth factor beta (TGF-β). Marker of cancer stem cells. It has a crucial role in angiogenesis, making it an important protein for tumor growth, survival and metastasis. Plasma levels of soluble CD105 have been shown to correlate with metastasis patients with breast cancer. | 5 | [17] |
| CD146 (MCAM) | Endothelial cells, pericytes, smooth muscle cells, follicular DC, melanoma cells, subpopulation of activated T-cells, marrow stromal cells (MSCs) | Cell adhesion molecule involved in the induction of epithelial-to-mesenchymal transition in breast cancer. Associated with high-grade tumors in breast cancer. | 7 | [16] |
| Proteins detected at low level, MFI 20–400 | ||||
| CD24 | B-cells, granulocytes, epithelial cells, monocytes, neuroblasts | Cell adhesion molecule, high levels in breast cancer tissue has been associated with poor prognosis. | 7 | [15] |
| CD31 (PECAM-1) | Monocytes, platelets, granulocytes, endothelial cells, lymphocyte subsets, and epithelial cells | Platelet endothelial cell adhesion molecule (PECAM-1). Used as marker of angiogenesis. | 5 | [29] |
| CD40 | B-cells, monocytes, macrophages, follicular DCs, endothelial cells, fibroblasts, and keratinocytes | Costimulatory protein found on antigen-presenting cells and is required for their activation. High expression correlates with overall survival in various types of cancer. | 5 | [30] |
| CD41b | Platelets and megakaryocytes | Platelet marker, cell adhesion. | 7 | [31] |
| CD49e (Integrin alpha 5) | Thymocytes, T-cells, early activated B-cells, monocytes, platelets, fibroblasts, endothelial, and epithelial cells | Member of the integrin family. CD49e associates with CD29 (integrin β1 chain) to form the fibronectin receptor (Integrin α5β1). Integrin α5β1 has a role in carcinogenesis and cancer progression, and has been shown to be up-regulated in breast cancer cells, while functioning as tumor suppressors in some types of cancer and in cancer cell lines. | 6 | [32, 33] |
| MCSP (CSPG4) | Some cancer cells | Transmembrane proteoglycan. Expressed in breast cancer. High level in breast cancer tissue has been suggested to correlate with poor outcome. | 6 | [34, 61] |
| HLA-DR-DP-DQ | Antigen presenting cells and activated T cells | MHC class II, antigen presentation | 7 | |
Cellular expression adapted from [61]