Next Article in Journal
miRNA Expression Signatures of Therapy Response in Squamous Cell Carcinomas
Next Article in Special Issue
Role of Omentin in Obesity Paradox in Lung Cancer
Previous Article in Journal
The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
Previous Article in Special Issue
Calcitriol in the Presence of Conditioned Media from Metastatic Breast Cancer Cells Enhances Ex Vivo Polarization of M2 Alternative Murine Bone Marrow-Derived Macrophages
Article

The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells

1
Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway
2
The Proteomics Facility of the University of Bergen (PROBE), University of Bergen, N-5021 Bergen, Norway
3
Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(1), 62; https://doi.org/10.3390/cancers13010062
Received: 30 November 2020 / Revised: 22 December 2020 / Accepted: 23 December 2020 / Published: 28 December 2020
(This article belongs to the Special Issue Microenvironment and Cancer Progression)
Normal blood cells are formed in the bone marrow by a process called hematopoiesis. This process is supported by a network of non-hematopoietic cells including connective tissue cells, blood vessel cells and bone-forming cells. However, these cells can also support the growth of cancer cells, i.e., hematological malignancies (e.g., leukemias) and cancers that arise in another organ and spread to the bone marrow. Two of these cancer-supporting normal cells are bone-forming osteoblasts and a subset of connective tissue cells called mesenchymal stem cells. One mechanism for their cancer support is the release of proteins that support cancer cell proliferation and progression of the cancer disease. Our present study shows that both these normal cells release a wide range of proteins that support cancer cells, and inhibition of this protein-mediated cancer support may become a new strategy for cancer treatment.
Mesenchymal stem cells (MSCs) and osteoblasts are bone marrow stromal cells that contribute to the formation of stem cell niches and support normal hematopoiesis, leukemogenesis and development of metastases from distant cancers. This support is mediated through cell–cell contact, release of soluble mediators and formation of extracellular matrix. By using a proteomic approach, we characterized the protein release by in vitro cultured human MSCs (10 donors) and osteoblasts (nine donors). We identified 1379 molecules released by these cells, including 340 proteins belonging to the GO-term Extracellular matrix. Both cell types released a wide range of functionally heterogeneous proteins including extracellular matrix molecules (especially collagens), several enzymes and especially proteases, cytokines and soluble adhesion molecules, but also several intracellular molecules including chaperones, cytoplasmic mediators, histones and non-histone nuclear molecules. The levels of most proteins did not differ between MSCs and osteoblasts, but 82 proteins were more abundant for MSC (especially extracellular matrix proteins and proteases) and 36 proteins more abundant for osteoblasts. Finally, a large number of exosomal proteins were identified. To conclude, MSCs and osteoblasts show extracellular release of a wide range of functionally diverse proteins, including several extracellular matrix molecules known to support cancer progression (e.g., metastases from distant tumors, increased relapse risk for hematological malignancies), and the large number of identified exosomal proteins suggests that exocytosis is an important mechanism of protein release. View Full-Text
Keywords: cancer; bone marrow; osteoblasts; mesenchymal stem cells; protein; proteomics; conditioned medium; extracellular matrix; exosome cancer; bone marrow; osteoblasts; mesenchymal stem cells; protein; proteomics; conditioned medium; extracellular matrix; exosome
Show Figures

Figure 1

MDPI and ACS Style

Aasebø, E.; Birkeland, E.; Selheim, F.; Berven, F.; Brenner, A.K.; Bruserud, Ø. The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells. Cancers 2021, 13, 62. https://doi.org/10.3390/cancers13010062

AMA Style

Aasebø E, Birkeland E, Selheim F, Berven F, Brenner AK, Bruserud Ø. The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells. Cancers. 2021; 13(1):62. https://doi.org/10.3390/cancers13010062

Chicago/Turabian Style

Aasebø, Elise; Birkeland, Even; Selheim, Frode; Berven, Frode; Brenner, Annette K.; Bruserud, Øystein. 2021. "The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells" Cancers 13, no. 1: 62. https://doi.org/10.3390/cancers13010062

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop