differential mechanical response of mesenchymal stem cells and fibroblasts to tumor-secreted soluble factors微分的力学响应间充质干细胞和成纤维细胞tumor-secreted溶性因素.pdfVIP

Differential Mechanical Response of Mesenchymal Stem Cells and Fibroblasts to Tumor-Secreted Soluble Factors 1 1 2 1,3 Daniel J. McGrail , Deepraj Ghosh , Nhat D. Quach , Michelle R. Dawson * 1 School of Chemical Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America, 2 School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America, 3 The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States of America Abstract The progression of neoplastic malignancies is a complex process resulting not only from the accumulation of mutations within tumor cells, but also modulation of the tumor microenvironment. Recent advances have shown that the recruitment and subsequent heterotypic interactions of stromal cells—including fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs)—are crucial for carcinogenesis. Though extensive work has been done analyzing the signals that recruit these cells, the governing mechanical properties have not been fully investigated. Here, we report that despite their initial similarities, MSCs respond not only faster but also more dramatically to pro-migratory tumor-secreted soluble factors. Utilizing multiple particle tracking microrheology to probe the cytoskeletal mechanical properties, we show that MSCs stiffen completely within one hour, three times faster than fibroblasts. In addition, unlike fibroblasts, MSCs exposed to tumor-secreted soluble factors display a functionally different phenotype characterized by morphological elongation, decrea