title: 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.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China and.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China, Department of Anatomy and Histology, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Han-Zhen
authors.initials: HZ
authors.lastname: Xiong
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Zhou
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Lu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China, nfydlxn@126.com.
authors.forename: Xue-Nong
authors.initials: XN
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse