Characterization of side populations in HNSCC: highly invasive, chemoresistant and abnormal Wnt signaling.
Side Population (SP) cells, a subset of Hoechst-low cells, are enriched with stem cells. Originally, SP cells were isolated from bone marrow but recently have been found in various solid tumors and cancer cell lines that are clonogenic in vitro and tumorigenic in vivo. In this study, SP cells from lymph node metastatic head and neck squamous cell carcinoma (HNSCC) cell lines were examined using flow cytometry and Hoechst 3342 efflux assay. We found that highly metastatic HNSCC cell lines M3a2 and M4e contained more SP cells compared to the low metastatic parental HNSCC cell line 686LN. SP cells in HNSCC were highly invasive in vitro and tumorigenic in vivo compared to non-SP cells. Furthermore, SP cells highly expressed ABCG2 and were chemoresistant to Bortezomib and etoposide. Importantly, we found that SP cells in HNSCC had abnormal activation of Wnt/beta-catenin signaling as compared to non-SP cells. Together, these findings indicate that SP cells might be a major driving force of head and neck tumor formation and metastasis. The Wnt/beta-catenin signaling pathway may be an important target for eliminating cancer stem cells in HNSCC.
Song
Jun
J
Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California Los Angeles School of Dentistry, Los Angeles, California, United States of America.
Chang
Insoon
I
Chen
Zhuo
Z
Kang
Mo
M
Wang
Cun-Yu
CY
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000627:therapeutic use; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001897:Boronic Acids; D009363:Neoplasm Proteins; D011719:Pyrazines; D051153:Wnt Proteins; D051176:beta Catenin; D000069286:Bortezomib; D005047:Etoposide