title: Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth.
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.
authors: School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors: Wei
authors: W
authors: Zhu
authors: Ling
authors: L
authors: Huang
authors: Yahong
authors: Y
authors: Li
authors: Hui
authors: H
authors: Qian
authors: Xiuhong
authors: X
authors: Shan
authors: Yongmin
authors: Y
authors: Yan
authors: Fei
authors: F
authors: Mao
authors: Xiaosheng
authors: X
authors: Wu
authors: Wen-Rong
authors: WR
authors: Xu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D049109:Cell Proliferation; D002470:Cell Survival; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition; D019204:GTP-Binding Proteins; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008279:Magnetic Resonance Imaging; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D055153:Stem Cell Niche; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D017077:Culture Media, Conditioned; D047908:Intracellular Signaling Peptides and Proteins; C100494:RTKN protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C066737:RHOA protein, human; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein