Cell adhesiveness serves as a biophysical marker for metastatic potential
| Autor: | Aditya Kumar, Hannah Carter, Jesse K. Placone, Adam J. Engler, Kevin Chen, Afsheen Banisadr, Alyssa Chiang, Enio Hodzic, Benjamin Yeoman, Pranjali Beri, Anna Popravko, Stephanie I. Fraley, Parag Katira |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Culture Techniques Focal adhesion assembly Datasets as Topic Cell Separation Microtubules 0302 clinical medicine Cell Movement 2.1 Biological and endogenous factors RNA-Seq Aetiology Neoplasm Metastasis Cytoskeleton Cancer education.field_of_study Tumor Chemistry Adhesion Flow Cytometry Progression-Free Survival Cell biology Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis Female Stromal cell Population Oncology and Carcinogenesis Breast Neoplasms Article Cell Line Focal adhesion 03 medical and health sciences Cell Line Tumor Spheroids Cellular Breast Cancer Genetics Cell Adhesion Humans Oncology & Carcinogenesis Cell adhesion education Neoplastic Focal Adhesions Coculture Techniques 030104 developmental biology Gene Expression Regulation Cell culture Cancer cell Cellular Spheroids |
| Zdroj: | Cancer Res Cancer research, vol 80, iss 4 |
| Popis: | Tumors are heterogeneous and composed of cells with different dissemination abilities. Despite significant effort, there is no universal biological marker that serves as a metric for metastatic potential of solid tumors. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Adhesion strength is heterogeneous even among cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups; when cultured under stromal conditions, this adhesion phenotype was stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Weakly adherent cells displayed increased migration in both two-dimensional and three-dimensional migration assays; this was maintained for several days in culture. Subpopulations did not show differences in expression of proteins involved in the focal adhesion complex but did exhibit intrinsic focal adhesion assembly as well as contractile differences that resulted from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity. In human breast tumors, expression of genes associated with the weakly adherent population resulted in worse progression-free and disease-free intervals. These data suggest that adhesion strength could potentially serve as a stable marker for migration and metastatic potential within a given tumor population and that the fraction of weakly adherent cells present within a tumor could act as a physical marker for metastatic potential. Significance: Cancer cells exhibit heterogeneity in adhesivity, which can be used to predict metastatic potential. |
| Databáze: | OpenAIRE |
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