Mikaela M Mallin, Nicholas Kim, Mohammad Ikbal Choudhury, Se Jong Lee, Steven S An, Sean X Sun, Konstantinos Konstantopoulos, Kenneth J Pienta, Sarah R Amend
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引用次数: 3
Abstract
Although metastasis is the leading cause of cancer deaths, it is quite rare at the cellular level. Only a rare subset of cancer cells (~ 1 in 1.5 billion) can complete the entire metastatic cascade: invasion, intravasation, survival in the circulation, extravasation, and colonization (i.e. are metastasis competent). We propose that cells engaging a Polyaneuploid Cancer Cell (PACC) phenotype are metastasis competent. Cells in the PACC state are enlarged, endocycling (i.e. non-dividing) cells with increased genomic content that form in response to stress. Single-cell tracking using time lapse microscopy reveals that PACC state cells have increased motility. Additionally, cells in the PACC state exhibit increased capacity for environment-sensing and directional migration in chemotactic environments, predicting successful invasion. Magnetic Twisting Cytometry and Atomic Force Microscopy reveal that cells in the PACC state display hyper-elastic properties like increased peripheral deformability and maintained peri-nuclear cortical integrity that predict successful intravasation and extravasation. Furthermore, four orthogonal methods reveal that cells in the PACC state have increased expression of vimentin, a hyper-elastic biomolecule known to modulate biomechanical properties and induce mesenchymal-like motility. Taken together, these data indicate that cells in the PACC state have increased metastatic potential and are worthy of further in vivo analysis.
期刊介绍:
The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.