Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells.

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.

• Authors: Chao Zhang, Chang Zhou, Xiao-Jin Wu, Min Yang, Zhao-Hui Yang, Han-Zhen Xiong, Chun-Ping Zhou, Yan-Xia Lu, Yuan Li, Xue-Nong Li
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 12 Pg. 2771-7 (Dec 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 25269803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• AC133 Antigen
• Antigens, CD
• Glycoproteins
• PROM1 protein, human
• Peptides
• Prom1 protein, mouse

Topics

• AC133 Antigen
• Animals
• Antigens, CD (metabolism)
• Blotting, Western
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (metabolism, pathology)
• Electrophoresis, Gel, Two-Dimensional
• Female
• Fetal Blood (cytology, metabolism)
• Glycoproteins (metabolism)
• Hematopoietic Stem Cells (metabolism, pathology)
• Humans
• Liver Neoplasms (metabolism, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Peptides (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays