Organizing the Cellular and Molecular Heterogeneity in High-Grade Serous Ovarian Cancer by Mass Cytometry
Abstract
Primary ovarian cancer (OC) represents a complex set of stem cell and cancer cell phenotypes embedded in a mixture of stromal and infiltrating immune cells. This grant develops techniques and approaches using mass cytometry that organize the heterogeneity within and between patient tumors to enlighten mechanisms and clinical opportunities in the apparent chaotic structure of the cancer. (1) A preliminary mass cytometry OC dataset by a social clustering strategy finds cell neighborhoods in high dimensional space reveals that 18 out of 20 samples had clusters of apparent stem-cell expressing deterministic combinations of stem cell markers. (2) Two high dimensional antibody panels were optimized and assembled to interrogate the tumor and immune cell compartments. (3) Indivumed (Hamburg Germany) is established as source for acquiring high quality HG-SOC primary specimens from single-cell dissociated tumors obtained within 3 hours of resection. (4) A QC procedure was established that surveys tumor samples (including epithelial, mesenchymal and immune cells) prior to their resection (using Abs against cleaved cCaspase 3, cleaved cPARP, vimentin, E-cadherin and CD45) to focus resection procedures on viable non necrotic tissue. (5) Eight key cell lines which bear remarkable genetic similarity to primary HG-SOC tumors have been obtained [1] as standards for primary tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA599601
Entities
People
- Garry P. Nolan
Organizations
- Stanford University