BackgroundMesenchymal stem cells (MSCs) in tumors have emerged as progenitors involved in stroma formation and metastasis of cancers, partially owing to their abilities to differentially express paracrine factors related to the proliferation and invasion of cancer cells. In this regard, increasing evidence has shown that MSCs have impacts on the malignancy of colon cancer, however, the underpinning mechanisms by which MSCs promote cancer metastasis remain elusive.MethodsTo investigate the crosstalk between adipose-derived MSCs (AMSCs) isolated from adipose tissues and colon cancer cells, a co-culture transwell model of AMSCs and colon cancer cells was employed, and the activation of Wnt signaling and paracrine factors in colon cancer cells and AMSCs were measured.ResultsThe results showed that AMSCs could enhance the metastatic capacity of colon cancer cells with an elevated expression of mesenchymal-epithelial transition (EMT)-associated genes in a contact-dependent manner. Reciprocally, colon cancer cells were able to induce AMSCs to produce metastasis-related factors and cytokines, such as FGF10, VEGFC and matrix metalloproteinases (MMPs) in part through a mechanism of an activation of Wnt signaling, by which these factors in turn activate Wnt signaling of colon cancer cells. Intriguingly, an inhibition of Wnt signaling leads a reduced capacity of invasion and colony formation of colon cancer cells in vitro, and the tumorigenicity of cancer cells in a murine model.ConclusionsThese findings thus suggest that the crosstalk between the Wnt signaling of cancer cells and paracrine factors of AMSCs has an implication in colon cancer malignancy. This study thus uncovers a novel Wnt-paracrine factors mediated-crosstalk between colon cancer cells and AMSCs in cancer malignancy.

The oxidative stresses are a major insult in pulmonary injury such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality. Mesenchymal stem cells (MSCs) hold a promise in treatments of many human diseases, mainly owing to their capacities of immunoregulation and antioxidative activity. The strong immunoregulatory role of human placental MSCs of fetal origin (hfPMSCs) has been previously demonstrated; their antioxidant activity, however, has yet been interrogated. In this report, we examined the antioxidative activity of hfPMSCs by accessing the ability to scavenge oxidants and radicals and to protect alveolar epithelial cells from antioxidative injury using both a cell coculture model and a conditioned culture medium (CM) of hfPMSCs. Results showed a comparable antioxidative capacity of the CM with 100 μM of vitamin C (VC) in terms of the total antioxidant capacity (T-AOC), scavenging abilities of free radicals DPPH, hydroxyl radical (·OH), and superoxide anion radical (O2-), as well as activities of antioxidant enzymes of SOD and GSH-PX. Importantly, both of the CM alone and cocultures of hfPMSCs displayed a protection of A549 alveolar epithelial cells from oxidative injury of 600 μM hydrogen peroxide (H2O2) exposure, as determined in monolayer and transwell coculture models, respectively. Mechanistically, hfPMSCs and their CM could significantly reduce the apoptotic cell fraction of alveolar epithelial A549 cells exposed to H2O2, accompanied with an increased expression of antiapoptotic proteins Bcl-2, Mcl-1, Nrf-2, and HO-1 and decreased proapoptotic proteins Bax, caspase 3, and Keap1, in comparison with naïve controls. Furthermore, hfPMSCs-CM (passage 3) collected from cultures exposed an inhibition of the Nrf2/Keap1/ARE signaling pathway which led to a significant reduction in caspase 3 expression in A549 cells, although the addition of Nrf2 inhibitor ML385 had no effect on the antioxidative activity of hfPMSCs-CM. These data clearly suggested that hfPMSCs protected the H2O2-induced cell oxidative injury at least in part by regulating the Nrf2-Keap1-ARE signaling-mediated cell apoptosis. Our study thus provided a new insight into the antioxidative mechanism and novel functions of hfPMSCs as antioxidants in disease treatments, which is warranted for further investigations.

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