ABSTRACT
The identification of side population (SP) cells in several cancer studies has been proved to be involved in the treatment failure (chemotherapy) and tumor relapse. Here we have sorted 7% of side population (SP) cells from lung adenocarcinoma by Hoechst 33342 dye expulsion method. Further, the characterization of sorted SP cells showed cancer stem like properties such as transcriptional upregulation of stemness genes (OCT-4, SOX2 and NANOG), ATP binding cassette (ABC) transporter protein (ABCG2) and enhanced level of stem cell surface markers such as CD133 and CD44. Therefore, the aforesaid properties of lung adenocarcinoma SP cells play a significant and functional role in tumor invasion, metastasis, chemotherapeutic drug resistance and tumor recurrence in lung cancer.
Subject(s)
Adenocarcinoma of Lung/metabolism , Lung Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Side-Population Cells/metabolism , AC133 Antigen/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Adenocarcinoma of Lung/pathology , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Female , Humans , Hyaluronan Receptors/metabolism , Lung Neoplasms/pathology , Male , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Octamer Transcription Factor-3/metabolism , Tumor Cells, CulturedABSTRACT
The aim of this study was to observe dynamic changes in immunological parameters and levels of inflammatory factors from pre-radiotherapy to post-radiotherapy in patients with esophageal cancer, and to evaluate the related clinical prognosis. In all, 110 patients with esophageal cancer who underwent radiotherapy were enrolled. Before radiotherapy, post-radiotherapy, and 3 months after radiotherapy, the percentages of T lymphocyte subsets and natural killer (NK) cells in peripheral blood were detected using flow cytometry. The levels of serum inflammatory factors were measured with the enzyme-linked immunosorbent assay (ELISA). Thirty peripheral blood samples from healthy people were similarly analysed as the control. Before radiotherapy, the percentages of CD4+ and CD8+ T cells and NK cells, and the CD4+/CD8+ rate in esophageal cancer patients were significantly different from those in the healthy control group (P < 0.001); the levels of inflammatory factors were increased significantly (P < 0.001). The percentages of the above cells and the levels of inflammatory factors also differed statistically significantly between pre- and post-radiotherapy (P < 0.001) in the esophageal cancer patients. Three months after radiotherapy, the percentages of CD3+ (P = 0.453), CD4+ (P = 0.108), and CD8+ T cells (P = 0.163) and NK cells (P = 0.103) had recovered to the level before radiotherapy; and the levels of TNF-α (P = 0.101), IL-6 (P = 0.302) and IL-8 (P = 0.250) were also restored. After radiotherapy, alterations in immunological parameters were associated with the irradiation volume and the myelosuppression condition. Patients with recovered immunological parameters showed a longer median survival time than those with poor recovery of immunological parameters. For esophageal cancer patients who were immunosuppressive and had an activated inflammatory response before radiotherapy, radiotherapy aggravated these symptoms, and this aggravation was positively associated with myelosuppression and irradiation volume. In addition, recovery of the immunological parameters indicated better prognosis.
Subject(s)
Esophageal Neoplasms/immunology , Esophageal Neoplasms/radiotherapy , Inflammation Mediators/metabolism , Inflammation/pathology , Adult , Aged , Esophageal Neoplasms/pathology , Female , Humans , Immunosuppression Therapy , Killer Cells, Natural/immunology , Male , Middle Aged , Prognosis , Survival Analysis , T-Lymphocyte Subsets/immunologyABSTRACT
Breast cancer has become the most popular malignant tumors in females. Breast cancer stem cells (BCSCs) play an important role in metastasis and recurrence. Previous study showed close correlation between miR-200c and behavioral regulation of breast cancer stem cells. This study aimed to investigate differential expression of miR-200c in breast cancer stem cells, and its role in regulation tumor formation property. DNA microchip assay and qRT-PCR analyzed differential expression of microRNA between BCSCs and non-tumor formation NTG cells. Bioinformatics and luciferase reporter gene assay determined targeted site of miR-200c. MiR mimic and inhibitor were transfected to change miR-200c expression level, followed by Western Blot for detecting BMI1 gene expression. Cell clonal assay determined cell proliferation, whilst tumor xenograft was performed to analyze tumor formation potency. MiR-200c was down-regulated in BCSCs compared to NTG cells (P<0.05). Bioinformatics and luciferase reporter gene assay attributed BMI1 gene as targeting site of miR-200c. Transfection of miR-200c and inhibitor altered miR-200c expression. Results showed that miR-200c could suppress BMI1 expression, and suppressed proliferation and tumor formation rate (P<0.05). Compared to NTG cells, BCSCs has significantly down-regulated expression of miR-200c. BCSCs facilitate BMI1 gene expression via inhibiting miR-200c expression, further elevating BCSCs proliferation and tumor formation potency.