title: Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6.
abstract: Multipotent mesenchymal stem cells (MSCs) have been isolated from several tumors and are implicated to play critical roles to increase malignant cell growth, invasion and metastasis. Here, we show that the MSC-like cells were isolated from human colon cancer tissues. These isolated hCC-MSCs (human colon cancer-derived mesenchymal stem cells) shared similar characteristic features with bone marrow-derived MSCs, which include cell morphology, surface antigens and specific gene expression. Additionally, the hCC-MSCs could differentiate into osteocytes or adipocytes under appropriate culture conditions. The conditioned medium collected from the cultured hCC-MSCs was shown to enhance the migration and invasive activity of HCT-116 colon cancer cells in vitro. Besides, transplantation of HCT-116 cells along with hCC-MSCs in nude mice increased the tumor growth and metastasis. Further study revealed that IL-6 present in the hCC-MSC-conditioned medium sufficiently induced the levels of Notch-1 and CD44 in HCT-116 and HT-29 cells, which contribute to enhance tumorigenic activity of HCT-116 and HT-29 cells. By using immunohistochemical staining, the intense co-expression of IL-6, Notch-1 and CD44 was predominantly detected in human colon cancer tissues. Taken together, our findings suggest the importance of the IL-6/Notch-1/CD44 signaling axis in the interaction between hCC-MSCs and colon cancer cells.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Jen-Tsun
authors.initials: JT
authors.lastname: Lin
authors.forename: Jeng-Yi
authors.initials: JY
authors.lastname: Wang
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Hong-Chang
authors.initials: HC
authors.lastname: Chen
authors.forename: Tung-Hao
authors.initials: TH
authors.lastname: Chang
authors.forename: Bi-Wen
authors.initials: BW
authors.lastname: Su
authors.forename: Pey-Jium
authors.initials: PJ
authors.lastname: Chang
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D010011:Osteocytes / Q000166:cytology; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018960:Hyaluronan Receptors; C508600:IL6 protein, human; D015850:Interleukin-6; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
keywords: CD44; Colon cancer; IL-6; Mesenchymal stem cells; Notch-1