Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice.
Tumor microenvironment in carcinomas recruits mesenchymal cells with an abnormal proangiogenic and invasive phenotype. It is not clear whether mesenchymal tumor cells (MTCs) derive from the activation of mature fibroblasts or from their stem cell precursors. However, stromal cell activation in tumors resembles in several aspects the mesenchymal rearrangement which normally occurs during reparative processes such as wound healing. Mesenchymal stem cells (MSCs) play a crucial role in developmental and reparative processes and have extraordinary proangiogenic potential, on the basis of which they are thought to show great promise for the treatment of ischemic disorders. Here, we show that MTCs have proangiogenic potential and that they share the transcriptional expression of the best-known proangiogenic factors with MSCs. We also found that MTCs and MSCs have the same molecular signature for stemness-related genes, and that when co-implanted with cancer cells in syngeneic animals MSCs determine early tumor appearance, probably by favoring the angiogenic switch. Our data (1) reveal crucial aspects of the proangiogenic phenotype of MTCs, (2) strongly suggest their stem origin and (3) signal the risk of therapeutic use of MSCs in tumor-promoting conditions.
Galiè
M
M
Department of Morphological and Biomedical Sciences, Anatomy and Histology Section, University of Verona, Verona, Italy. mirco@anatomy.univr.it
Konstantinidou
G
G
Peroni
D
D
Scambi
I
I
Marchini
C
C
Lisi
V
V
Krampera
M
M
Magnani
P
P
Merigo
F
F
Montani
M
M
Boschi
F
F
Marzola
P
P
Orrù
R
R
Farace
P
P
Sbarbati
A
A
Amici
A
A
D042501:Angiogenic Proteins / Q000096:biosynthesis*; D000818:Animals; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014185:Transplantation, Isogeneic
D042501:Angiogenic Proteins