Mimicking the tumor microenvironment: Fibroblasts reduce miR-29b expression and increase the motility of ovarian cancer cells in a co-culture model
| Autor: | Luiz Antonio Lupi, Danillo Pinhal, Amanda de Oliveira Pinto Ribeiro, Flávia Karina Delella, Mariana Medeiros, Luiz Gustavo de Almeida Chuffa, Guilherme Ribeiro Romualdo |
|---|---|
| Přispěvatelé: | Universidade Estadual Paulista (Unesp) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Biophysics Down-Regulation Motility Cell motility Biology Biochemistry Cell Line Extracellular matrix 03 medical and health sciences 0302 clinical medicine Cancer-Associated Fibroblasts Ovarian cancer Cell Movement Cell Line Tumor microRNA Tumor Microenvironment medicine Humans Viability assay CAF Molecular Biology SKOV-3 cells Ovarian Neoplasms Tumor microenvironment MicroRNA Cell migration Cell Biology Fibroblasts medicine.disease Coculture Techniques Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Cancer research Female Co-culture |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 0006-291X |
| Popis: | Made available in DSpace on 2019-10-06T17:11:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-13 Ovarian cancer (OC) is a highly prevalent gynecological malignancy worldwide. Throughout ovarian carcinogenesis, the crosstalk between cellular components of the microenvironment, including tumor cells and fibroblasts, is proposed to play critical roles in cancer progression. The dysregulation of microRNA expression is also a pronounced feature of the OC. The screening of microRNAs, mainly those involved in OC microenvironment, could have diagnostic and/or therapeutic potential for this malignancy. Thus, we assessed the influence of fibroblasts on microRNA expression and the motility of OC cells. To achieve this goal, SKOV-3 cancer cells were co-cultured with human normal fibroblasts derived from primary culture (FP-96). Cell viability, expression of tumor suppressor microRNAs and oncomiRs by RT-qPCR, cell migration by wound healing assay and analysis of MMP-2 activity by zymography were performed in SKOV-3 cells. Moreover, α-smooth muscle actin (α-SMA) expression was evaluated by Western blot in FP-96 fibroblasts. Notably, the co-culture downregulated the tumor suppressor miR-29b and increased migration of SKOV-3 cells. In addition, co-culture increased the activity of MMP-2, which is a miR-29 target, and accounted for extracellular matrix remodeling and augmented cellular motility. Concomitantly, the co-culture system induced α-SMA expression in FP-96 fibroblasts, the commonly expressed marker in cancer-associated fibroblasts (CAFs). Our findings suggest that the potential crosstalk between OC cells and fibroblasts in tumor microenvironment may play a key role in the progression of OC. Sao Paulo State University (UNESP) Institute of Biosciences Department of Morphology Sao Paulo State University (UNESP) Institute of Biosciences Department of Genetics Sao Paulo State University (UNESP) Institute of Biosciences Department of Anatomy Sao Paulo State University (UNESP) Institute of Biosciences Department of Morphology Sao Paulo State University (UNESP) Institute of Biosciences Department of Genetics Sao Paulo State University (UNESP) Institute of Biosciences Department of Anatomy |
| Databáze: | OpenAIRE |
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