Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells.
Chenxi TianYing HuangKarl R ClauserSteffen RickeltAllison N LauSteven A CarrMatthew G Vander HeidenRichard O HynesPublished in: Nature communications (2021)
Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studies on enriched ECM from samples of progressive PDAC stages reveal that the C-terminal prodomains of fibrillar collagens are partially uncleaved in PDAC ECM, suggesting reduced procollagen C-proteinase activity. We further show that the enzyme responsible for procollagen C-proteinase activity, bone morphogenetic protein1 (BMP1), selectively suppresses tumor growth and metastasis in cells expressing high levels of COL1A1. Although BMP1, as a secreted proteinase, promotes fibrillar collagen deposition from both cancer cells and stromal cells, only cancer-cell-derived procollagen cleavage and deposition suppresses tumor malignancy. These studies reveal a role for cancer-cell-derived fibrillar collagen in selectively restraining tumor growth and suggest stratification of patients based on their tumor epithelial collagen I expression when considering treatments related to perturbation of fibrillar collagens.
Keyphrases
- extracellular matrix
- mass spectrometry
- drug delivery
- papillary thyroid
- wound healing
- multiple sclerosis
- signaling pathway
- mesenchymal stem cells
- end stage renal disease
- ejection fraction
- induced apoptosis
- type iii
- tissue engineering
- newly diagnosed
- single cell
- chronic kidney disease
- liquid chromatography
- systematic review
- cell cycle arrest
- ms ms
- squamous cell carcinoma
- gene expression
- case control
- high performance liquid chromatography
- electronic health record
- machine learning
- bone regeneration
- randomized controlled trial
- binding protein
- dna binding
- gas chromatography
- artificial intelligence
- cancer therapy
- drug induced
- deep learning
- tandem mass spectrometry