Limits...
Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas.

Wu J, Mu Q, Thiviyanathan V, Annapragada A, Vigneswaran N - Int. J. Oncol. (2014)

Bottom Line: Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC.Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array.Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA‑HNSCC cells and not in the ALDHneg cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA.

ABSTRACT
Fanconi anemia (FA) patients have an increased risk of head and neck squamous cell carcinoma (HNSCC) at a higher rate with no apparent risk factors. HNSCC of FA patients is an aggressive tumor characterized by multifocal origin, early metastases and frequent recurrences. Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC. The Aldefluor assay was used to characterize and isolate CSC with high aldehyde dehydrogenase (ALDH) activity (ALDHpos) in cell lines derived from FA and sporadic HNSCC. Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array. Tumor cell-derived FA and sporadic HNSCC were examined for their ability to form tumorspheres in vitro. Stem-like cell population in FA and sporadic HNSCC in human and mouse xenograft tumors were evaluated using ALDH isoform 1 (ALDH1) immunohistochemistry. FA‑HNSCC cell lines harbor a greater proportion of ALDHpos cells (15-31%) compared to sporadic HNSCC (10%). Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA‑HNSCC cells and not in the ALDHneg cells. FA‑HNSCC cell lines revealed enhanced in vitro tumorsphere formation compared to sporadic HNSCC cells. A higher percentage of ALDH1pos tumor cells are noted in the human and mouse xenograft tumors of FA‑HNSCC compared to sporadic HNSCC tumors. FA‑HNSCC are highly enriched for CSC and may serve as a model to develop CSC-targeted therapies for HNSCC.

Show MeSH

Related in: MedlinePlus

Representative images of ALDH1pos cells in (A and D) Fanconi anemia (FA), and (B) sporadic, (A and B) human primary, and (C and D) mouse xenograft head and neck squamous cell carcinoma (HNSCC) tumor sections. Both (A) human primary and (D) mouse xenograft FA-HNSCC tumor sections exhibit greater fraction of ALDH1pos cells than (B) sporadic HNSCC tumor section. Immunohistochemical staining for ALDH isoform 1 (ALDH1) in (A and B) primary and (D) xenograft tumor sections. (C) Hematoxylin and eosin stained section of orthoptic mouse tongue xenograft of FA-HNSCC. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4215586&req=5

f4-ijo-45-06-2365: Representative images of ALDH1pos cells in (A and D) Fanconi anemia (FA), and (B) sporadic, (A and B) human primary, and (C and D) mouse xenograft head and neck squamous cell carcinoma (HNSCC) tumor sections. Both (A) human primary and (D) mouse xenograft FA-HNSCC tumor sections exhibit greater fraction of ALDH1pos cells than (B) sporadic HNSCC tumor section. Immunohistochemical staining for ALDH isoform 1 (ALDH1) in (A and B) primary and (D) xenograft tumor sections. (C) Hematoxylin and eosin stained section of orthoptic mouse tongue xenograft of FA-HNSCC. Scale bar, 100 μm.

Mentions: Tumor cells positive for ALDH1 were noted in three of the five sporadic HNSCC tissue sections. Less than 10% of the tumor cells stained positive for ALDH1 in sporadic HNSCC whereas >25% of tumor cells are positive for ALDH1 in FA-HNSCC tissue section (Fig. 4). Interestingly, the FA-HNSCC tumor xenograft sections exhibited similar patterns of ALDH1 expression as its parental tumor. Moreover, ALDH1-positivity was noted in individual and small groups (3–5 cells/group) of tumor cells in sporadic HNSCC tumor sections. In contrast, multiple large foci of tumor cells express ALDH1 in FA-HNSCC sample and its corresponding tumor xenograft (Fig. 4).


Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas.

Wu J, Mu Q, Thiviyanathan V, Annapragada A, Vigneswaran N - Int. J. Oncol. (2014)

Representative images of ALDH1pos cells in (A and D) Fanconi anemia (FA), and (B) sporadic, (A and B) human primary, and (C and D) mouse xenograft head and neck squamous cell carcinoma (HNSCC) tumor sections. Both (A) human primary and (D) mouse xenograft FA-HNSCC tumor sections exhibit greater fraction of ALDH1pos cells than (B) sporadic HNSCC tumor section. Immunohistochemical staining for ALDH isoform 1 (ALDH1) in (A and B) primary and (D) xenograft tumor sections. (C) Hematoxylin and eosin stained section of orthoptic mouse tongue xenograft of FA-HNSCC. Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215586&req=5

f4-ijo-45-06-2365: Representative images of ALDH1pos cells in (A and D) Fanconi anemia (FA), and (B) sporadic, (A and B) human primary, and (C and D) mouse xenograft head and neck squamous cell carcinoma (HNSCC) tumor sections. Both (A) human primary and (D) mouse xenograft FA-HNSCC tumor sections exhibit greater fraction of ALDH1pos cells than (B) sporadic HNSCC tumor section. Immunohistochemical staining for ALDH isoform 1 (ALDH1) in (A and B) primary and (D) xenograft tumor sections. (C) Hematoxylin and eosin stained section of orthoptic mouse tongue xenograft of FA-HNSCC. Scale bar, 100 μm.
Mentions: Tumor cells positive for ALDH1 were noted in three of the five sporadic HNSCC tissue sections. Less than 10% of the tumor cells stained positive for ALDH1 in sporadic HNSCC whereas >25% of tumor cells are positive for ALDH1 in FA-HNSCC tissue section (Fig. 4). Interestingly, the FA-HNSCC tumor xenograft sections exhibited similar patterns of ALDH1 expression as its parental tumor. Moreover, ALDH1-positivity was noted in individual and small groups (3–5 cells/group) of tumor cells in sporadic HNSCC tumor sections. In contrast, multiple large foci of tumor cells express ALDH1 in FA-HNSCC sample and its corresponding tumor xenograft (Fig. 4).

Bottom Line: Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC.Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array.Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA‑HNSCC cells and not in the ALDHneg cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA.

ABSTRACT
Fanconi anemia (FA) patients have an increased risk of head and neck squamous cell carcinoma (HNSCC) at a higher rate with no apparent risk factors. HNSCC of FA patients is an aggressive tumor characterized by multifocal origin, early metastases and frequent recurrences. Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC. The Aldefluor assay was used to characterize and isolate CSC with high aldehyde dehydrogenase (ALDH) activity (ALDHpos) in cell lines derived from FA and sporadic HNSCC. Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array. Tumor cell-derived FA and sporadic HNSCC were examined for their ability to form tumorspheres in vitro. Stem-like cell population in FA and sporadic HNSCC in human and mouse xenograft tumors were evaluated using ALDH isoform 1 (ALDH1) immunohistochemistry. FA‑HNSCC cell lines harbor a greater proportion of ALDHpos cells (15-31%) compared to sporadic HNSCC (10%). Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA‑HNSCC cells and not in the ALDHneg cells. FA‑HNSCC cell lines revealed enhanced in vitro tumorsphere formation compared to sporadic HNSCC cells. A higher percentage of ALDH1pos tumor cells are noted in the human and mouse xenograft tumors of FA‑HNSCC compared to sporadic HNSCC tumors. FA‑HNSCC are highly enriched for CSC and may serve as a model to develop CSC-targeted therapies for HNSCC.

Show MeSH
Related in: MedlinePlus