Identification of Ligands Selectively Targeting Breast Cancer Stem Cells via Combinatorial Chemical Library Screening

dc.contributor.advisorLee, Jiyong
dc.creatorLong, Chao
dc.date.accessioned2020-04-02T21:23:10Z
dc.date.available2020-04-02T21:23:10Z
dc.date.created2018-08
dc.date.issued2018-08
dc.date.submittedAugust 2018
dc.date.updated2020-04-02T21:23:10Z
dc.description.abstractCancer stem cells (CSCs), also known as tumor-initiating cells (TICs), play critical roles in the resistance to anti-cancer therapies, tumor metastasis and tumor relapse. An innovative synthetic binder to cancer stem cells would provide not only a chemical tool to study the mechanism of cancer stem cells, but also become a lead ligand for imaging, diagnoses or therapeutics targeting cancer stem cells. Herein, a synthetic peptoid ligand CL-1-19-1 that selectively binds to cancer stem cell subpopulation over non-CSC subpopulations of breast cancer was identified via a cellbased high throughput screening from a one-bead-one-compound (OBOC) combinatorial chemical library. CL-1-19-1 was verified to bind to CD24⁻/CD44⁺/ALDH⁺ cancer stem cell phenotype of MCF-7, MDA-MB-231, and BT549 respectively. CL-1-19-1-immobilized beads can also be utilized as a synthetic tool for the isolation of cancer stem cell subpopulation from ovarian cancer and prostate cancer cell lines. CL-1-19-1-bound population of cancer cells displayed increased expressions of stemness-associated transcription factors, such as SOX2, KLF4, C-myc, and Nanog. Furthermore, the CL-1-19-1-bound population demonstrated a higher tumor growth rate in vivo, as well as larger tumor size and cells from the tumors exhibited stronger expressions of cancer stem cell markers and more migratory activity. In conclusion, CL1-19-1 has been identified as the first synthetic binder of breast, ovarian and prostate CSCs, thus having high prospects as a chemical tool for isolating cancer stem cells from various solid cancer types including breast, ovarian, and prostate.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10735.1/7782
dc.language.isoen
dc.rights©2018 Chao Long. All Rights Reserved.
dc.subjectBiochemistry
dc.subjectBreast—Cancer
dc.subjectProstate—Cancer
dc.subjectStem cells
dc.subjectHigh throughput screening (Drug development)
dc.subjectMetastasis
dc.subjectTumors
dc.titleIdentification of Ligands Selectively Targeting Breast Cancer Stem Cells via Combinatorial Chemical Library Screening
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentChemistry
thesis.degree.grantorThe University of Texas at Dallas
thesis.degree.levelDoctoral
thesis.degree.namePHD

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