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Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth
- Source :
- Cell Cycle. 10:3198-3207
- Publication Year :
- 2011
- Publisher :
- Informa UK Limited, 2011.
-
Abstract
- In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on "reprogramming" of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression.
- Subjects :
- Vascular Endothelial Growth Factor A
Cell signaling
Epithelial-Mesenchymal Transition
Cell Survival
MAP Kinase Signaling System
Angiogenesis
Chick Embryo
Biology
Chorioallantoic Membrane
Mice
GTP-Binding Proteins
Image Processing, Computer-Assisted
Animals
Humans
Epithelial–mesenchymal transition
Stem Cell Niche
Molecular Biology
Cell Proliferation
Mice, Inbred BALB C
Neovascularization, Pathologic
Cell growth
Mesenchymal stem cell
Intracellular Signaling Peptides and Proteins
Mesenchymal Stem Cells
Neoplasms, Experimental
U937 Cells
Cell Biology
Magnetic Resonance Imaging
Xenograft Model Antitumor Assays
Coculture Techniques
In vitro
Cell biology
Tumor progression
Culture Media, Conditioned
Apoptosis Regulatory Proteins
rhoA GTP-Binding Protein
Reprogramming
Developmental Biology
Subjects
Details
- ISSN :
- 15514005 and 15384101
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Cell Cycle
- Accession number :
- edsair.doi.dedup.....7f366775855b0bbf8fb0e4efd449aad8