title: Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo.
abstract: Nowadays, some evidences demonstrate that human mesenchymal stem cells (hMSCs) favor tumor growth; however, others show that hMSCs can suppress tumorigenesis and tumor growth. With the indeterminateness of the effect of hMSCs on tumors, we investigated the effect of hMSCs on lung cancer cell line A549 and esophageal cancer cell line Eca-109 in vitro and in vivo. Our results revealed that hMSCs inhibited the proliferation and invasion of A549 and Eca-109 cells, arrested tumor cells in the G1 phase of the cell cycle and induced the apoptosis of tumor cells in vitro by using a co-culture system and the hMSCs-conditioned medium. However, animal study showed that hMSCs enhanced tumor formation and growth in vivo. Western blotting and immunoprecipitation data showed that the expressions of proliferating cell nuclear antigen (PCNA), Cyclin E, phospho-retinoblastoma protein (pRb), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL, and matrix metalloproteinase 2 (MMP-2) were downregulated and the formation of Cyclin E-cyclin-dependent kinase 2 (CDK2) complexes was inhibited in the tumor cells treated with the hMSCs-conditioned medium. According to the observation of tumor mass and the result of microvessel density (MVD), we found that the promoting role of hMSCs on tumor growth was related with the increase of tumor vessel formation. Our present study suggests that hMSCs have a contradictory effect on tumor cell growth between in vitro and in vivo, and therefore, the exploitation of hMSCs in new therapeutic strategies should be cautious under the malignant conditions.
authors: Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan, PR China. qilutianh@163.com
authors: Lin Li Hui
authors: LL
authors: Tian
authors: Weiming
authors: W
authors: Yue
authors: Feng
authors: F
authors: Zhu
authors: Shuhai
authors: S
authors: Li
authors: Wenjun
authors: W
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D017077:Culture Media, Conditioned; D019927:Cyclin E; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D051020:bcl-X Protein; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2