SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with colorectal cancer progression

ABSTRACTColorectal cancer (CRC) is a malignancy with high incidence and poor prognosis. It is urgent to identify valuable biomarkers for early diagnosis and potent therapeutic targets. It has been reported that SATB1 is associated with the malignant progression in CRC. To explore the role of SATB1 in CRC progression and the underlying mechanism, we evaluated the expression of SATB1 in the paired CRC tissues with immunohistochemistry. The results showed that the expression of SATB1 in lymph node metastasis was higher than that in primary lesion, and that in distant organ metastasis was higher than that in primary lesion. The retrospective analysis showed that patients with high expression of SATB1 had a significantly worse prognosis than those with negative and moderate expression. In vitro experiments that employing SATB1 over-expressing and depleted CRC cell lines confirmed that SATB1 contributes to cell proliferation and colonization, while inhibiting cell motility. Furthermore, the tissue immunofluorescence assay, Co-IP and Western blot were conducted to reveal that SATB1 induced translocation of β-catenin and formed a protein complex with it in the nuclei. In conclusion, SATB1 mediated tumor colonization and β-catenin nuclear localization are associated with the malignant progression and poor prognosis of CRC

Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor

Abstract Background Although many reports show that various kinds of stem cells have the ability to recover function in premature ovarian aging, few studies have looked at stem cell treatment of natural ovarian aging (NOA). We designed this experimental study to investigate whether human amniotic mesenchymal stem cells (hAMSCs) retain the ability to restore ovarian function, and how hAMSCs work in this process. Methods To build the NOA mouse model, the mice were fed for 12–14 months normally with young fertile female mice as the normal control group (3–5 months old). Hematoxylin and eosin staining permitted follicle counting and showed the ovarian tissue structure. An enzyme-linked immunosorbent assay was used to detect the serum levels of the sex hormones estradiol (E2), anti-mullerian hormone (AMH), and follicle-stimulating hormone (FSH). The proliferation rate and marker expression level of human ovarian granule cells (hGCs) (ki67, AMH, FSH receptor, FOXL2, and CYP19A1) were measured by flow cytometry (FACS). Cytokines (growth factors) were measured by a protein antibody array methodology. After hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were co-cultured with hGCs, proliferation (ki67) and apoptosis (Annexin V) levels were analyzed by FACS. After HGF and EGF were injected into the ovaries of natural aging mice, the total follicle numbers and hormone levels were tested. Results After the hAMSCs were transplanted into the NOA mouse model, the hAMSCs exerted a therapeutic activity on mouse ovarian function by improving the follicle numbers over four stages. In addition, our results showed that hAMSCs significantly promoted the proliferation rate and marker expression level of ovarian granular cells that were from NOA patients. Meanwhile, we found that the secretion level of EGF and HGF from hAMSCs was higher than other growth factors. A growth factor combination (HGF with EGF) improved the proliferation rate and inhibited the apoptosis rate more powerfully after a co-culture with hGCs, and total follicle numbers and hormone levels were elevated to a normal level after the growth factor combination was injected into the ovaries of the NOA mouse model. Conclusions These findings provide insight into the notion that hAMSCs play an integral role in resistance to NOA. Furthermore, our present study demonstrates that a growth factor combination derived from hAMSCs plays a central role in inhibiting ovarian aging. Therefore, we suggest that hAMSCs improve ovarian function in natural aging by secreting HGF and EGF

Additional file 2: Figure S2. of Different therapeutic effects of cells derived from human amniotic membrane on premature ovarian aging depend on distinct cellular biological characteristics

is showing distinction of cytokine levels between hAMSCs and hAECs. (A) Distinction of chemotactic factor levels between hAMSCs and hAECs. (B) Difference of apoptosis factor levels between hAMSCs and hAECs. (C) Difference of inflammatory factor levels between hAMSCs and hAECs. (TIF 8400 kb

Additional file 1: Figure S1. of Different therapeutic effects of cells derived from human amniotic membrane on premature ovarian aging depend on distinct cellular biological characteristics

is showing characterization of hAMSCs and hAECs tested. (A) Phenotype of CD105, CD29, CD44, CD73, CD90, CD34, and CD45 in hAMSCs detected by flow cytometry. (B) hAECs differentiate into adipocytes (Oil Red), osteoblasts (Alizarin red) and chondroblasts (Alcian blue) under standard in-vitro differentiating conditions. Scale bars = 10 μm. (C) Expression level of EpCam, CD44, CD73, CD105, and CD166 in hAECs detected by flow cytometry. (TIF 6049 kb

Additional file 1: of Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor

Figure S1. An antibody microarray to test the level of the growth factors derived from the hAMSCs. (A) Antibody microarray analysis of the growth factor secretion from the hAMSCs and the control group. (B) Five growth factors were selected in accordance with the standard criteria that the fold-change was greater than or equal to 8 and was statistically significant (p < 0.01). (TIF 26685 kb