Mechanisms of differentiation of omental-adipose stromal cells promoted by gastric cancer cells / 中国肿瘤临床

Objective:To investigate whether the omental-adipose stromal cells (O-ASCs) exposing to gastric cancer-conditioned medi-um (CM) could be inducted to differentiate into carcinoma-associated fibroblasts (CAFs) and the effect of ERK signaling pathway in the process. Methods: We identified O-ASCs by examining their ability to differentiate osteogenic and adipogenic lineages and through flow cytometry. O-ASCs were co-cultured with MGC803 and SGC7901CM. The expression of CAFs markers (α-SMA, FSP-1, and vimentin) and paracrine factors (VEGFA, TGF-β1, FAP, and SDF-1) were evaluated by RT-PCR and Western blot. In vitro cultures of O-ASCs were divided into three groups:the control, SGC7901-CM, and SGC7901-CM+U0126 groups. Cells were collected after 12 h. West-ern blot was performed to evaluate the expression ofα-SMA, FSP-1, ERK, and p-ERK1/2. Results:The primary cells were O-ASCs. The expression levels of CAFs markers (α-SMA, FSP-1, and vimentin) and O-ASC paracrine factors (VEGFA, TGF-β1, FAP, and SDF-1) clearly in-creased (P0.05), while the ex-pression of p-ERK1/2,α-SMA, and FSP-1 significantly improved (P0.05), while the expression levels of p-ERK1/2,α-SMA, and FSP-1 decreased (P<0.05). Conclusion:O-ASCs participate in the peritoneal metastasis of gastric cancer through differentiation by CAF and paracrine factors. The ERK signaling pathway is important in the differentiation of O-ASCs towards CAFs.

Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells. MATERIALS AND METHODS: CD45– and CD31– double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively. RESULTS: CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients. CONCLUSION: ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.

Effect of Cytokines Secreted by Human Adipose Stromal Cells on Endothelial Cells / 华中科技大学学报（医学）（英德文版）

To isolate and culture adipose stromal cells (ASCs), and study the effect of cytokines secreted by ASCs on endothelial cells, human adipose tissue was digested with collagenase type Ⅰ solution and ASCs were derived by culture. The cells surface phenotype was examined by flow cytometry. ELISA was used to detect the secretion of VEGF, HGF, SDF-1 α and RT-PCR was employed to detect the expression of their mRNA. Then the ASC medium was utilized to culture human umbilical vein endothelial cells ECV304. Cells were counted by hemacytometer to determine the proliferation and Annexin V/PI was employed for the examination of the apoptosis rate of ECV304. ASCs were derived by culture and expressed CD34, CD105 while they did not express CD31 or CD45. ASCs secreted cytokines such as VEGF, HGF and SDF-1 α so the ASC medium could stimulate proliferation and counteract apoptosis of endothelial cells (P＜0.05). Bcl-2 mRNA was also found to be up-regulated in the endothelial cells. It is concluded that ASCs can secrete cytokines and has significant effect on the proliferation of endothelial cells and apoptosis.