Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.
There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Feng-Feng
FF
Sun
The General Hospital of Chengdu Military Region Chengdu 610083, Sichuan Province, China.
Yong-He
YH
Hu
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Lv-Ping
LP
Xiong
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Xiao-Yun
XY
Tu
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Ji-Hua
JH
Zhao
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Sheng-Song
SS
Chen
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Juan
J
Song
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Xiao-Qun
XQ
Ye
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D018874:Spheroids, Cellular / Q000473:pathology*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
CD133; Cancer stem cell; GST-π; LRP; MRP1; multidrug resistance