Leading edge or tumor core: Intratumor cancer stem cell niches in oral cavity squamous cell carcinoma and their association with stem cell function.

Autor: Chowdhury FN; Department of Otolaryngology, University of Colorado Denver School of Medicine (UCDSOM), Aurora, CO 80045, USA., Reisinger J; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Gomez KE; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Chimed TS; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Thomas CM; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, University Health Network/Princess Margaret Cancer Centre, Toronto, ON M4Y 2X5, Canada., Le PN; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Miller B; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Morton JJ; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Nieto CM; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA., Somerset HL; Department of Pathology, UCDSOM, Aurora, CO 80045, USA., Wang XJ; Department of Pathology, UCDSOM, Aurora, CO 80045, USA., Keysar SB; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA. Electronic address: stephen.keysar@ucdenver.edu., Jimeno A; Department of Otolaryngology, University of Colorado Denver School of Medicine (UCDSOM), Aurora, CO 80045, USA; Division of Medical Oncology, Department of Medicine, UCDSOM, Aurora, CO 80045, USA. Electronic address: antonio.jimeno@ucdenver.edu.
Jazyk: angličtina
Zdroj: Oral oncology [Oral Oncol] 2019 Nov; Vol. 98, pp. 118-124. Date of Electronic Publication: 2019 Oct 03.
DOI: 10.1016/j.oraloncology.2019.09.011
Abstrakt: Objectives: To describe differences in cancer stem cell (CSC) presence and behavior associated with their intratumor compartment of origin using a patient-derived xenograft (PDX) model of oral cavity squamous cell carcinoma (OCSCC).
Materials and Methods: Four HPV-negative OCSCC PDX cases were selected (CUHN004, CUHN013, CUHN096, CUHN111) and the percentage of CSCs (ALDH + CD44 high ) was measured in the tumor Leading Edge (LE) and Core compartments of each PDX tumor case via fluorescence activated cell sorting (FACS). The fraction of cells in the proliferative phase was measured by Ki-67 labelling index of paraffin embedded tissue. The proliferation and invasion of LE versus Core CSCs were compared using sphere and Matrigel invasion assays, respectively.
Results: Both CUHN111 and CUHN004 demonstrate CSC enrichment in their LE compartments while CUHN013 and CUHN096 show no intratumor difference. Cases with LE CSC enrichment demonstrate greater Ki-67 labelling at the LE. CSC proliferative potential, assessed by sphere formation, reveals greater sphere formation in CUHN111 LE CSCs, but no difference between CUHN013 LE and Core CSCs. CUHN111 CSCs do not demonstrate an intratumor difference in invasiveness while CUHN013 LE CSCs are more invasive than Core CSCs.
Conclusion: A discrete intratumor CSC niche is present in a subset of OCSCC PDX tumors. The CSC functional phenotype with regard to proliferation and invasion is associated with the intratumor compartment of origin of the CSC: LE or Core. These individual functional characteristics appear to be modulated independently of one another and independently of the presence of an intratumor CSC niche.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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