1. Biomedical Engineering Division, Department of Electronic and Computer Engineering, Ngee Ann Polytechnic, Singapore;2. Institute of Bioengineering and Nanotechnology, A*STAR, Singapore;3. NUS Graduate Programme in Bioengineering, NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore;4. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;5. BioSystems and Micromechanics, Singapore‐MIT Alliance for Research and Technology, Singapore;6. Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou, China;7. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;8. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;9. Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA, USA;10. Cancer Science Institute of Singapore, National University of Singapore, Singapore;11. School of Medicine, Division of Hematology and Oncology, Loma Linda University, CA, USA;12. Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, Singapore;13. Mechanobiology Institute, National University of Singapore, Singapore
Abstract:
Cancer initiating cells (CICs) have been the focus of recent anti‐cancer therapies, exhibiting strong invasion capability via potentially enhanced ability to remodel extracellular matrices (ECM). We have identified CICs in a human breast cancer cell line, MX‐1, and developed a xenograft model in SCID mice. We investigated the CICs' matrix‐remodeling effects using Second Harmonic Generation (SHG) microscopy to identify potential phenotypic signatures of the CIC‐rich tumors. The isolated CICs exhibit higher proliferation, drug efflux and drug resistant properties in vitro; were more tumorigenic than non‐CICs, resulting in more and larger tumors in the xenograft model. The CIC‐rich tumors have less collagen in the tumor interior than in the CIC‐poor tumors supporting the idea that the CICs can remodel the collagen more effectively. The collagen fibers were preferentially aligned perpendicular to the CIC‐rich tumor boundary while parallel to the CIC‐poor tumor boundary suggesting more invasive behavior of the CIC‐rich tumors. These findings would provide potential translational values in quantifying and monitoring CIC‐rich tumors in future anti‐cancer therapies.
CIC‐rich tumors remodel the collagen matrix more than CIC‐poor tumors.
