Abstract
BackgroundNew 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.ResultsWe 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.ConclusionThese 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.
Highlights
New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth
We found that the cell number of the conditioned media incubated 10T1/2 cells increased more significantly than the control, and maximum cell number was increased in the invasive (MDAMB-231 and PaCa-2) cell line-derived-condition media (CM) in comparison to the non-invasive (MCF-7) cell line-derived CM (Fig. 1D)
Since we found that human tumor cell-derived conditioned media is able to differentiate the mouse mesenchymal stem cells into pericytes, we investigated whether PDGF-AB/BB existed in the Tumor cell-derived conditioned media (TCM), and is required for the mesenchymal to pericyte transition (MPT)
Summary
New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor cells assign neighboring blood vessels to support their own blood supply for oxygen and nutrients and for intravasation (to enter into the blood vessels) and extravasation (metastatic spread) through promoting pathologic neovascularization/angiogenesis [1,2,3] This event is potentiated by tumor cells through the production of diffusible angiogenic factors [4,5,6]. New blood vessel formation/angiogenesis and remodeling of the vessel is a complex event and is dependent on proliferation, differentiation, mobilization and attachment of endothelial cells (ECs) and mural cells (MCs) with different phenotypic variants such vascular smooth muscle cells (VSMCs) and pericytes (PCs) in an autocrine-paracrine manner [7,8,9,10,11]. We are interested to explore whether the tumor cells have the ability to differentiate, recruit and interact with PCs to establish new blood vessels for their maintenance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
