title: Differential remodeling of extracellular matrices by breast cancer initiating cells.
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.
authors.affiliation: Biomedical Engineering Division, Department of Electronic and Computer Engineering, Ngee Ann Polytechnic, 535 Clementi Road, Singapore, 599489.|Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, 138669.|NUS Graduate Programme in Bioengineering, NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117597.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Anju M
authors.initials: AM
authors.lastname: Raja
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, 138669.|BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore, 138602.
authors.forename: Shuoyu
authors.initials: S
authors.lastname: Xu
authors.affiliation: BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore, 138602.|Institute of Laser and Optoelectronics Technology, Fujian Normal University, Fuzhou, 350007, China.
authors.forename: Shuangmu
authors.initials: S
authors.lastname: Zhuo
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, 138669.
authors.forename: Dean C S
authors.initials: DC
authors.lastname: Tai
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, 138669.
authors.forename: Wanxin
authors.initials: W
authors.lastname: Sun
authors.affiliation: BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore, 138602.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.|Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Peter T C
authors.initials: PT
authors.lastname: So
authors.affiliation: Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Roy E
authors.initials: RE
authors.lastname: Welsch
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, 28 Medical Drive, Singapore, 117456.|School of Medicine, Division of Hematology and Oncology, Loma Linda University, CA, 92354, USA.
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, 138669. hanry_yu@nuhs.edu.sg.|NUS Graduate Programme in Bioengineering, NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117597. hanry_yu@nuhs.edu.sg.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. hanry_yu@nuhs.edu.sg.|BioSystems and Micromechanics, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #04-13/14 Enterprise Wing, Singapore, 138602. hanry_yu@nuhs.edu.sg.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. hanry_yu@nuhs.edu.sg.|Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, Singapore, 117597. hanry_yu@nuhs.edu.sg.|Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore, 117411. hanry_yu@nuhs.edu.sg.
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D003094:Collagen / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008853:Microscopy; D008942:Mitoxantrone / Q000378:metabolism / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*
chemical_list: D004317:Doxorubicin; D003094:Collagen; D008942:Mitoxantrone
keywords: Second Harmonic Generation microscopy; breast cancer; cancer initiating cells; collagen