Paracrine recruitment and activation of fibroblasts by c-Myc expressing breast epithelial cells through the IGFs/IGF-1R axis.
Breast
/ pathology
Breast Neoplasms
/ pathology
Cancer-Associated Fibroblasts
/ drug effects
Cell Differentiation
/ drug effects
Cell Line
Coculture Techniques
Culture Media, Conditioned
/ pharmacology
Epithelial Cells
/ metabolism
Female
Humans
Insulin-Like Growth Factor Binding Protein 6
/ genetics
Insulin-Like Growth Factor I
/ genetics
Insulin-Like Growth Factor II
/ genetics
Neoplasm Invasiveness
/ pathology
Podophyllotoxin
/ analogs & derivatives
Primary Cell Culture
Proto-Oncogene Proteins c-myc
/ metabolism
RNA, Small Interfering
/ metabolism
Receptor, IGF Type 1
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Tumor Cells, Cultured
Tumor Microenvironment
IGFs/IGF-1R axis
Urokinase receptor
breast cancer cell invasion
c-Myc
cancer-associated fibroblasts
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 11 2019
15 11 2019
Historique:
received:
30
07
2018
revised:
26
06
2019
accepted:
30
07
2019
pubmed:
6
8
2019
medline:
18
2
2020
entrez:
6
8
2019
Statut:
ppublish
Résumé
Fibroblasts are among the most abundant stromal cells in the tumor microenvironment (TME), progressively differentiating into activated, motile, myofibroblast-like, protumorigenic cells referred to as Cancer-Associated Fibroblasts (CAFs). To investigate the mechanisms by which epithelial cells direct this transition, the early stages of tumorigenesis were exemplified by indirect cocultures of WI-38 or human primary breast cancer fibroblasts with human mammary epithelial cells expressing an inducible c-Myc oncogene (MCF10A-MycER). After c-Myc activation, the conditioned medium (CM) of MCF10A-MycER cells significantly enhanced fibroblast activation and mobilization. As this was accompanied by decreased insulin-like growth factor binding protein-6 (IGFBP-6) and increased insulin-like growth factor-1 and IGF-II (IGF-I, IGF-II) in the CM, IGFs were investigated as key chemotactic factors. Silencing IGFBP-6 or IGF-I or IGF-II expression in epithelial cells or blocking Insulin-like growth factor 1 receptor (IGF-1R) activity on fibroblasts significantly altered fibroblast mobilization. Exposure of WI-38 fibroblasts to CM from induced MCF10A-MycER cells or to IGF-II upregulated FAK phosphorylation on Tyr
Substances chimiques
Culture Media, Conditioned
0
IGF1 protein, human
0
IGF1R protein, human
0
IGF2 protein, human
0
Insulin-Like Growth Factor Binding Protein 6
0
MYC protein, human
0
Proto-Oncogene Proteins c-myc
0
RNA, Small Interfering
0
Insulin-Like Growth Factor I
67763-96-6
Insulin-Like Growth Factor II
67763-97-7
Receptor, IGF Type 1
EC 2.7.10.1
Podophyllotoxin
L36H50F353
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2827-2839Informations de copyright
© 2019 UICC.
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