The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma Determines Cancer Associated Fibroblast Growth.
Kyle H BondTakuto ChibaKieran P H WynneCalvin P H VarySunder Sims-LucasJeannine M CoburnLeif OxburghPublished in: Cancers (2021)
Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and is often caused by mutations in the oxygen-sensing machinery of kidney epithelial cells. Due to its pseudo-hypoxic state, ccRCC recruits extensive vasculature and other stromal components. Conventional cell culture methods provide poor representation of stromal cell types in primary cultures of ccRCC, and we hypothesized that mimicking the extracellular environment of the tumor would promote growth of both tumor and stromal cells. We employed proteomics to identify the components of ccRCC extracellular matrix (ECM) and found that in contrast to healthy kidney cortex, laminin, collagen IV, and entactin/nidogen are minor contributors. Instead, the ccRCC ECM is composed largely of collagen VI, fibronectin, and tenascin C. Analysis of single cell expression data indicates that cancer-associated fibroblasts are a major source of tumor ECM production. Tumor cells as well as stromal cells bind efficiently to a nine-component ECM blend characteristic of ccRCC. Primary patient-derived tumor cells bind the nine-component blend efficiently, allowing to us to establish mixed primary cultures of tumor cells and stromal cells. These miniature patient-specific replicas are conducive to microscopy and can be used to analyze interactions between cells in a model tumor microenvironment.
Keyphrases
- extracellular matrix
- single cell
- bone marrow
- poor prognosis
- rna seq
- high throughput
- mass spectrometry
- wound healing
- magnetic resonance
- induced apoptosis
- stem cells
- functional connectivity
- cell death
- optical coherence tomography
- cell cycle arrest
- cell therapy
- squamous cell
- label free
- computed tomography
- cell proliferation
- endoplasmic reticulum stress
- artificial intelligence
- neural network