Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1.
BACKGROUND
New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process.


RESULTS
We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells.


CONCLUSIONS
These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.
Dhar
Kakali
K
Cancer Research Unit, VA Medical Center, 4801 Linwood Blvd, Kansas City, Missouri 64128, USA.
Dhar
Gopal
G
Majumder
Monami
M
Haque
Inamul
I
Mehta
Smita
S
Van Veldhuizen
Peter J
PJ
Banerjee
Sushanta K
SK
Banerjee
Snigdha
S
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D017077:Culture Media, Conditioned; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D039942:Neuropilin-1 / Q000502:physiology*; D020286:Pericytes / Q000166:cytology*; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology*
D017077:Culture Media, Conditioned; D020574:Proto-Oncogene Proteins c-sis; D039942:Neuropilin-1