Abstract
Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis.
Highlights
Mesenchymal stem cells (MSCs) are multipotent cells that originate from bone marrow or other tissues
It was identified that the gastric cancer HGC‐27 cell line treated with one‐half Dulbecco's modified Eagle's medium (DMEM) and one‐half hBM‐MSC‐CM for 20 days exhibited increased tube formation compared with the HGC‐27 cells treated with DMEM alone (Fig. 1C)
Other studies have revealed that MSCs are able to promote tumor growth and metastasis, including in breast cancer [19,20,21,22], and that MSC‐like cells isolated from human colon cancer tissues can increase tumor growth and metastasis [23]
Summary
Mesenchymal stem cells (MSCs) are multipotent cells that originate from bone marrow or other tissues. MSCs can be recruited to a variety of tumors, including breast [2] and gastric cancer [3]. Chaturvedi et al [2] revealed that hypoxia‐inducible factors mediated the interactions of MSCs with breast cancer cells to promote metastasis. A study by Zhang et al [5] identified that MSCs were able to promote CXC chemokine receptor (CXCR) type 4‐mediated osteosarcoma growth and pulmonary metastasis by upregulating the expression of vascular epidermal growth factor (VEGF). The CXC chemokine ligand 16 and CXCR6 signaling pathway stimulates the conversion of MSCs into cancer‐associated fibroblasts, which facilitates prostate tumor metastasis [6]. Lymph vessels are an important component in lymph node metastasis, but the association between MSCs and lymph vessels remains unknown
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