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.

Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

“…MSCs appear to have a complex biology in other gastrointestinal cancers, including esophageal cancer, gastric cancer, and pancreatic carcinoma. Li et al [77] applied hMSCs together with esophageal cancer cells subcutaneously in nude mice. The authors showed that hMSCs could promote tumor growth with increased tumor vessel formation in vivo.…”

Effects of the two types of human cells on outgrowth of human glioma in rats

“…Recently, studies reported that MSCs promote cancer growth and metastasis (20,29). However, MSC cancer-suppressing effects have only been observed in a few reports (33,34); and most studies reported that migration of MSC leads to angiogenesis and tumor development (27,32). Moreover, extensive tropism of BMS cells to tumor was observed, which may be due to the BMS cells secreting a variety of substances such as stem cell factor, interleukins, and colony-stimulating factor-I (5,8).…”

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

“…The proposed use of MSCs in cancer therapies provoke strong disagreement in scientific community, due to opposite results for MSC promotion of tumor vascularization, promotion of cancer progression and the invasive tendency of tumors previously reported [28,[120][121][122]. In this contest, Li et al, 2011, inform about the dual role of human MSCs in tumor cell growth in vitro and in vivo. It was found that in vitro human MSCs inhibited the proliferation of A549 (lung cancer) and Eca-109 (esophageal cancer) cell lines and caused G1 phase cell cycle arrest and apoptosis.…”

“…It was found that in vitro human MSCs inhibited the proliferation of A549 (lung cancer) and Eca-109 (esophageal cancer) cell lines and caused G1 phase cell cycle arrest and apoptosis. On the other hand, human MSCs were also found to increase tumor formation and growth in experiments in vivo [123].…”