Human amniotic membrane-derived epithelial stem cells display anticancer activity in BALB/c female nude mice bearing disseminated breast cancer xenografts

Abstract

Abstract. Breast cancer is one of the most common malignant tumors and the leading cause of mortality among women. In this study, we propose a human stem cell transplantation strategy, an important method for treating various cancers, as a potential breast cancer therapy. To this end, we used human amniotic membrane-derived epithelial stem cells (hAECs) as a cell source for performing human stem cell transplantation. hAECs have multipotent differentiation abilities and possess high proliferative potential. We transplanted hAECs into female BALB/c nude mice bearing tumors originating from MDA-MB-231 breast cancer cells. Co-culturred hAECs and MDA-MB-231 cells at a ratio of 1:4 or 1:8 (tumor cells to stem cells) inhibited breast cancer cell growth by 67.29 and 67.33%, respectively. In the xenograft mouse model, tumor volumes were significantly decreased by 5-flurouracil (5-FU) treatment and two different ratios of hAECs (1:4 and 1:8) by 84.33, 73.88 and 56.89%, respectively. Treatment of nude mice with hAECs (1:4) produced remarkable antitumor effects without any sideeffects (e.g., weight loss, death and bruising) compared to the mice that received only 5-FU treatment. Tumor progression was significantly reduced by hAEC treatment compared to the xenograft model. On the other hand, breast tissues (e.g., the epidermis, dermis and reticular layer) appeared to be wellmaintained following treatment with hAECs. Taken together, these results provide strong evidence that hAECs can be used as a safe and effective cancer-targeting cytotherapy for treating breast cancer.

Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells via TGF-β1-mediated cell cycle arrest

“…In this study, results from a cytokine array revealed that hAECs released various cytokines which are able to induce G0/G1 cell cycle arrest, including TGF-β1 ( 22 ), GM-CSF ( 23 ), IL-8 ( 24 ), IL-6 ( 25 ), IL-1 ( 26 ), IFN-γ, TNF-α ( 27 ), TGF-β2 ( 28 ) and Smad 7 ( 29 ). Our results showed that the secretion of TGF-β1 derived from hAECs was abundant, this is consistent with the report of Kang et al showing the amount of TGF-β1 ranked first among those anticancer-associated factors ( 9 ). We used recombinant human TGF-β1 to imitate the function of hAEC-secreted TGF-β1 on EOC cells.…”

“…Niknejad et al reported that hAEC-conditioned medium (hAEC-CM) could induce apoptosis in HeLa cells and MDA-MB-231 cells in vitro ( 8 ). Kang et al showed that hAECs displayed anticancer activity in a breast cancer-bearing nude mouse model through both cell-to-cell contact and paracrine way ( 9 ). However, Mamede et al revealed adverse effects of amniotic membrane-extracted proteins on human cancer cell lines tested by MTT assay in vitro ( 10 ).…”

Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications

“…Mechanistically, the expression of telomerase hTERT in hAESCs is not detected, explaining why hAESCs do not generate tumors. Notably, several studies demonstrated that hAESCs could inhibit tumor cell growth and induce apoptosis of cancer cells, including HeLa cells and breast and ovarian cancer cells [ 94 , 95 , 96 ]. However, Yang et al reported that co-injection of hAESCs and Raji tumor cells into immunodeficient mice shows a similar survival duration when compared with the mice receiving only Raji cells, which indicated hAESCs have little effect on tumor growth [ 29 ].…”

Effects of Genetically Engineered Stem Cells Expressing Cytosine Deaminase and Interferon-Beta or Carboxyl Esterase on the Growth of LNCaP Prostate Cancer Cells

“…We confirmed the ability of HB1.F3.CD, HB1.F3.CD.IFN-β, or HB1.F3.CE cells to migrate toward LNCaP prostate cancer cells. The tumor-tropic effects of stem cells are generally attributed to growth factors and cytokines [30,31]. Real time-PCR analysis demonstrated that the LNCaP prostate cancer cells expressed several cytokines including VEGF, MCP-1, and SCF.…”