1. Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells.
- Author
-
Zhang C, Zhou C, Wu XJ, Yang M, Yang ZH, Xiong HZ, Zhou CP, Lu YX, Li Y, and Li XN
- Subjects
- AC133 Antigen, Animals, Blotting, Western, Colorectal Neoplasms metabolism, Electrophoresis, Gel, Two-Dimensional, Female, Fetal Blood cytology, Fetal Blood metabolism, Hematopoietic Stem Cells metabolism, Humans, Liver Neoplasms metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Antigens, CD metabolism, Cell Movement, Cell Proliferation, Colorectal Neoplasms pathology, Glycoproteins metabolism, Hematopoietic Stem Cells pathology, Liver Neoplasms secondary, Peptides metabolism
- Abstract
The tumour-specific 'pre-metastatic niche' has emerged as a potential driving force for tumour metastasis and has been confirmed using mouse models of cancer metastasis. Vascular endothelial growth factor receptor-1(+) hematopoietic progenitor cells (HPCs) have been shown to play an important role in metastasis, forming a 'pre-metastatic niche' at designated sites for distant tumour progression. Here, CD133+ human umbilical hematopoietic progenitor cells (HUHPCs) were purified from human umbilical cord blood and expanded in vitro. We studied the effects of CD133+ HUHPCs on the growth and metastasis of four colorectal cancer (CRC) cell lines by using cell-to-cell co-culture. Our results revealed that CD133+ HUHPCs promoted the proliferation and invasion of CRC cells in vitro and enhanced tumour growth and metastasis in vivo. Moreover, CD133+ HUHPCs were observed in the pre-metastatic liver tissue using immunohistochemical analysis after co-injection of SW480/EGFP(+) cells and HUHPCs. Further experiments were therefore conducted to uncover the molecular mechanisms by which CD133+ HUHPCs influenced colon carcinogenesis and cancer progression. Extracted proteins were separated using the two-dimensional difference in gel electrophoresis technology. Among the differentially expressed proteins, mitogen-activated protein 4 kinase 4, stromal cell-derived factor-1, matrix metallopeptidase 9, calumenin, peripherin, leucine zipper, putative tumour suppressor 1 and guanidinoacetate methyltransferase attracted our attention. Western blot analysis further confirmed the differential expression of these proteins. Altogether, these results suggest that CD133+ HUHPCs may induce proliferation or metastasis of CRC cells and impact their derived proteins by providing a pre-metastatic microenvironment., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF