Unique characteristics in fetal development include scar-less wound healing and the paucity of tumor formation. Recent studies have demonstrated that the embryonic microenvironment can reverse melanoma cells to a beni...Unique characteristics in fetal development include scar-less wound healing and the paucity of tumor formation. Recent studies have demonstrated that the embryonic microenvironment can reverse melanoma cells to a benign melanocyte phenotype. We bioengineered embryonic-like compositions and tested the anti-cancer activity of this material on a panel of skin cancer lines. To simulate the embryonic environment, neonatal fibroblasts were grown in hypoxic suspension cultures. The cells reverted back into multipotent stem cells as evidenced by the upregulation of SOX2, Oct4, NANOG, and KLF4 genes, and by the expression of stem cell-associated proteins including Nodal, Brachyury, Nestin, and Oct4. Cell Conditioned Media (CCM) and human Extracellular Matrix Proteins (hECM) produced by these cells were tested for their ability to reduce cell viability in skin cancer cell lines. In vitro studies with CCM and hECM show reduction in Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC) and melanoma cell number through upregulation of caspases and induction of apoptosis. In the chick allantoic membrane assay, melanoma load was reduced by up to 80% with hECM treatment compared to vehicle treated controls (p 0.05). Similar inhibition was seen with SCC cells. In a xenograft mouse model of subcutaneous melanoma, tumor growth was inhibited by 70% - 90%. These data suggest that CCM and hECM have anti tumor potential and might offer a new treatment strategy in skin cancer.展开更多
文摘Unique characteristics in fetal development include scar-less wound healing and the paucity of tumor formation. Recent studies have demonstrated that the embryonic microenvironment can reverse melanoma cells to a benign melanocyte phenotype. We bioengineered embryonic-like compositions and tested the anti-cancer activity of this material on a panel of skin cancer lines. To simulate the embryonic environment, neonatal fibroblasts were grown in hypoxic suspension cultures. The cells reverted back into multipotent stem cells as evidenced by the upregulation of SOX2, Oct4, NANOG, and KLF4 genes, and by the expression of stem cell-associated proteins including Nodal, Brachyury, Nestin, and Oct4. Cell Conditioned Media (CCM) and human Extracellular Matrix Proteins (hECM) produced by these cells were tested for their ability to reduce cell viability in skin cancer cell lines. In vitro studies with CCM and hECM show reduction in Squamous Cell Carcinoma (SCC), Basal Cell Carcinoma (BCC) and melanoma cell number through upregulation of caspases and induction of apoptosis. In the chick allantoic membrane assay, melanoma load was reduced by up to 80% with hECM treatment compared to vehicle treated controls (p 0.05). Similar inhibition was seen with SCC cells. In a xenograft mouse model of subcutaneous melanoma, tumor growth was inhibited by 70% - 90%. These data suggest that CCM and hECM have anti tumor potential and might offer a new treatment strategy in skin cancer.
