Bone marrow-derived cells contribute to NDEA-induced lung squamous cell carcinoma.

Abstract

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.

• Authors: Dan Luo, Dengqun Liu, Xiangdong Zhou, Shiming Yang, Chunlan Tang, Guoxiang Liu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 1 Pg. 145-54 (Feb 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23055190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ki-67 Antigen
• Phosphoproteins
• Trans-Activators
• Trp63 protein, mouse
• Green Fluorescent Proteins
• Diethylnitrosamine
• Keratins

Topics

• Animals
• Bone Marrow Cells (physiology)
• Bone Marrow Transplantation
• Carcinoma, Squamous Cell (chemically induced, metabolism, pathology)
• Cell Differentiation
• Cell Movement
• Cell Proliferation
• Cell Transformation, Neoplastic
• Diethylnitrosamine
• Epithelial Cells (physiology)
• Female
• Green Fluorescent Proteins
• Keratinocytes (pathology)
• Keratins (biosynthesis)
• Ki-67 Antigen (analysis)
• Lung Neoplasms (chemically induced, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Phosphoproteins (analysis)
• Stem Cells (physiology)
• Trans-Activators (analysis)