Bone marrow-derived cells contribute to NDEA-induced lung squamous cell carcinoma.
Bone marrow-derived stem cells (BMDCs) have the ability to differentiate into lung epithelial cells in response to damage; however, their role in squamous cell carcinoma (SCC) formation is unknown. This study aimed to determine whether BMDC-derived lung epithelial cells could contribute to SCC formation. A model of lung SCC induced with N-nitrosodiethylamine (NDEA) in recipient female mice transplanted with green fluorescent protein (GFP)-positive BMDCs from male donors was established. Incorporation of BMDCs in lung tissue was determined using immunohistochemistry and immunofluorescence to detect GFP expression and fluorescence in situ hybridization to Y chromosomes. BMDC appeared at three stages of lung SCC progression: metaplasia, dysplasia, and carcinoma. There was a significantly higher proportion of GFP-positive (GFP(+)) cells within SCC than was found in metaplasia and dysplasia 16 weeks post-transplantation (both P < 0.017); GFP(+) BMDCs were also observed in clusters within several SCC nests. Furthermore, most GFP(+) cells in SCC were pancytokeratin-positive (PCK(+)) epithelial cells, and some exhibited proliferative activity as determined by Ki67 staining (9.7 ± 3.92 %). The presence of GFP(+)Ki67(+)PCK(+) cells within SCC nests suggested that some donor BMDCs differentiated into proliferating epithelial cells. Finally, analysis of p63 expression, a marker of SCC cells, indicated that the presence of GFP(+)p63(+) cells (green) in inner parts of the SCC. These findings strongly suggest that BMDC-derived lung epithelial cells could participate in lung SCC formation and partially contribute to tumor growth, which might have significant potential implications for both clinical cancer therapy using BMDCs.
Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Dan
D
Luo
Dengqun
D
Liu
Xiangdong
X
Zhou
Shiming
S
Yang
Chunlan
C
Tang
Guoxiang
G
Liu
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004052:Diethylnitrosamine; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins; D015603:Keratinocytes / Q000473:pathology; D007633:Keratins / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000032:analysis; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000032:analysis
D019394:Ki-67 Antigen; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D049452:Green Fluorescent Proteins; D004052:Diethylnitrosamine; D007633:Keratins