Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative
Adrian Biddle,Xiao Liang,Luke Gammon,Bilal Fazil,Lisa J. Harper,Helena Emich,Daniela Elena Costea,Ian C. Mackenzie +7 more
Reads0
Chats0
TLDR
A need to define therapeutic targets that can eradicate both EMT and self-renewing CSC variants to achieve effective SCC treatment is suggested.Abstract:
Epithelial-to-mesenchymal transition (EMT) is an important driver of tumor invasion and metastasis, which causes many cancer deaths. Cancer stem cells (CSC) that maintain and initiate tumors have also been implicated in invasion and metastasis, but whether EMT is an important contributor to CSC function is unclear. In this study, we investigated whether a population of CSCs that have undergone EMT (EMT CSCs) exists in squamous cell carcinoma (SCC). We also determined whether a separate population of CSCs that retain epithelial characteristics (non-EMT CSCs) is also present. Our studies revealed that self-renewing CSCs in SCC include two biologically-distinct phenotypes. One phenotype, termed CD44(high)ESA(high), was proliferative and retained epithelial characteristics (non-EMT CSCs), whereas the other phenotype, termed CD44(high)ESA(low), was migratory and had mesenchymal traits characteristic of EMT CSCs. We found that non-EMT and EMT CSCs could switch their epithelial or mesenchymal traits to reconstitute the cellular heterogeneity which was characteristic of CSCs. However, the ability of EMT CSCs to switch to non-EMT character was restricted to cells that were also ALDH1(+), implying that only ALDH1(+) EMT cells had the ability to seed a new epithelial tumor. Taken together, our findings highlight the identification of two distinct CSC phenotypes and suggest a need to define therapeutic targets that can eradicate both of these variants to achieve effective SCC treatment.read more
Citations
More filters
Dissertation
Dissecting the role of iASPP, a novel crucial regulator of epidermal homeostasis, in squamous cell carcinoma
TL;DR: This paper aims to provide a chronology of the events leading up to and including the publication of this book and some of the key events that led to its publication.
Journal ArticleDOI
Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility.
Saroj Rajthala,Anjie Min,Himalaya Parajuli,Kala Chand Debnath,Borghild Ljøkjel,Kristin Marie Hoven,Arild Kvalheim,Stein Lybak,Evelyn Neppelberg,Olav Karsten Vintermyr,Anne Christine Johannessen,Dipak Sapkota,Daniela Elena Costea +12 more
TL;DR: In this article, the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC) was investigated.
Journal ArticleDOI
The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells.
Tarig Al-Hadi Osman,Himalaya Parajuli,Dipak Sapkota,Israa Abdulrahman Ahmed,Anne Ch. Johannessen,Anne Ch. Johannessen,Daniela Elena Costea,Daniela Elena Costea +7 more
TL;DR: In this article, the authors investigated the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell-like properties in oral squamous cell carcinoma (OSCC).
Journal Article
Effect of hydrogel stiffness on morphology and gene expression pattern of CD44high oral squamous cell carcinoma cells.
Hideo Shigeishi,Sho Yokoyama,Hiroshi Murodumi,Miyuki Sakuma,Hiroki Kato,Koichiro Higashikawa,Masaaki Takechi,Kouji Ohta,Masaru Sugiyama +8 more
TL;DR: Results indicated that CD44high OM-1 cells underwent mesenchymal to amoeboid transition (MAT) when cultured on laminin-coated softer hydrogel, suggesting that cofilin was associated with MAT in CD44 high OSCC cells.
Journal Article
CD44high/ESAlow squamous cell carcinoma cell-derived prostaglandin E2 confers resistance to 5-fluorouracil-induced apoptosis in CD44high/ESAhigh cells.
Hideo Shigeishi,Miho Hashikata,Sho Yokoyama,Miyuki Sakuma,Hiroshi Murozumi,Hiroki Kato,Mohammad Zeshaan Rahman,Sayaka Seino,Yasuki Ishioka,Kouji Ohta,Masaaki Takechi,Masaru Sugiyama +11 more
TL;DR: CD44high/ESAlow cells contribute to induction of resistance to 5-FU in CD44 high/ESAhigh cells through provision of PGE2, suggesting that CD44high / ESAlow cell-targeted therapy may be effective in treatment of HNSCC.
References
More filters
Journal ArticleDOI
Prospective identification of tumorigenic breast cancer cells
Muhammad Al-Hajj,Max S. Wicha,Adalberto Benito-Hernandez,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +5 more
TL;DR: The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival and strategies designed to target this population may lead to more effective therapies.
Journal ArticleDOI
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
Journal Article
Identification of a Cancer Stem Cell in Human Brain Tumors
Sheila K. Singh,Ian D. Clarke,Mizuhiko Terasaki,Victoria E. Bonn,Cynthia Hawkins,Jeremy A. Squire,Peter B. Dirks +6 more
TL;DR: The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.
Journal ArticleDOI
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
Christophe Ginestier,Min Hee Hur,Emmanuelle Charafe-Jauffret,Florence Monville,Julie Dutcher,Marty Brown,Jocelyne Jacquemier,Patrice Viens,Celina G. Kleer,Suling Liu,Anne F. Schott,Daniel F. Hayes,Daniel Birnbaum,Max S. Wicha,Gabriela Dontu +14 more
TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
Journal ArticleDOI
Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).