Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic prof
- PDF / 1,844,128 Bytes
- 12 Pages / 595.276 x 793.701 pts Page_size
- 12 Downloads / 170 Views
RESEARCH
Open Access
Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile Raphael Lis1†, Cyril Touboul1†, Najeeb M Halabi1, Abishek Sainath Madduri2, Denis Querleu3, Jason Mezey2, Joel A Malek4, Karsten Suhre5 and Arash Rafii1,2,6*
Abstract Background: The cross talk between the stroma and cancer cells plays a major role in phenotypic modulation. During peritoneal carcinomatosis ovarian cancer cells interact with mesenchymal stem cells (MSC) resulting in increased metastatic ability. Understanding the transcriptomic changes underlying the phenotypic modulation will allow identification of key genes to target. However in the context of personalized medicine we must consider inter and intra tumoral heterogeneity. In this study we used a pathway-based approach to illustrate the role of cell line background in transcriptomic modification during a cross talk with MSC. Methods: We used two ovarian cancer cell lines as a surrogate for different ovarian cancer subtypes: OVCAR3 for an epithelial and SKOV3 for a mesenchymal subtype. We co-cultured them with MSCs. Genome wide gene expression was determined after cell sorting. Ingenuity pathway analysis was used to decipher the cell specific transcriptomic changes related to different pro-metastatic traits (Adherence, migration, invasion, proliferation and chemoresistance). Results: We demonstrate that co-culture of ovarian cancer cells in direct cellular contact with MSCs induces broad transcriptomic changes related to enhance metastatic ability. Genes related to cellular adhesion, invasion, migration, proliferation and chemoresistance were enriched under these experimental conditions. Network analysis of differentially expressed genes clearly shows a cell type specific pattern. Conclusion: The contact with the mesenchymal niche increase metastatic initiation and expansion through cancer cells’ transcriptome modification dependent of the cellular subtype. Personalized medicine strategy might benefit from network analysis revealing the subtype specific nodes to target to disrupt acquired pro-metastatic profile. Keywords: Ovarian cancer, Mesenchymal stem cell, Transcriptome, Genomic modification, Metastasis
Background Ovarian cancer is the most deadly gynecologic cancer with most patients dying from diffuse peritoneal disease [1]. Defined steps involving changes of cancer cells’ phenotypes are implicated in the development of peritoneal * Correspondence: [email protected] † Equal contributors 1 Department of Genetic Medicine and Obstetrics and Gynecology, Stem cell and microenvironment laboratory, Weill Cornell Medical College in Qatar (WCMC-Q), Education City, Qatar Foundation, Qatar-Foundation PO: 24144, Doha, Qatar 2 Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA Full list of author information is available at the end of the article
carcinomatosis (reviewed in [2]). Many studies in the literature illustrate the existence of a cross talk between cancer and
Data Loading...
