title: Local alignment vectors reveal cancer cell-induced ECM fiber remodeling dynamics.
abstract: Invasive cancer cells interact with the surrounding extracellular matrix (ECM), remodeling ECM fiber network structure by condensing, degrading, and aligning these fibers. We developed a novel local alignment vector analysis method to quantitatively measure collagen fiber alignment as a vector field using Circular Statistics. This method was applied to human non-small cell lung carcinoma (NSCLC) cell lines, embedded as spheroids in a collagen gel. Collagen remodeling was monitored using second harmonic generation imaging under normal conditions and when the LKB1-MARK1 pathway was disrupted through RNAi-based approaches. The results showed that inhibiting LKB1 or MARK1 in NSCLC increases the collagen fiber alignment and captures outward alignment vectors from the tumor spheroid, corresponding to high invasiveness of LKB1 mutant cancer cells. With time-lapse imaging of ECM micro-fiber morphology, the local alignment vector can measure the dynamic signature of invasive cancer cell activity and cell-migration-induced ECM and collagen remodeling and realigning dynamics.
authors.affiliation: Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.
authors.forename: Byoungkoo
authors.initials: B
authors.lastname: Lee
authors.affiliation: Cancer Biology Graduate Program, Emory University, Atlanta, GA, USA.|Department of Hematology and Oncology, Emory University, Atlanta, GA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Konen
authors.affiliation: Cancer Biology Graduate Program, Emory University, Atlanta, GA, USA.|Department of Hematology and Oncology, Emory University, Atlanta, GA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Wilkinson
authors.affiliation: Department of Hematology and Oncology, Emory University, Atlanta, GA, USA.|Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Marcus
authors.affiliation: Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D003094:Collagen; C105547:MARK1 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases