Uveal melanoma cells elicit retinal pericyte phenotypical and biochemical changes in an in vitro model of coculture

Autor: Alfio Distefano, Mario Salmeri, Gabriella Lupo, Anna Longo, Angela Maria Amorini, Guido Zanghì, Giovanni Giurdanella, Carmelina Daniela Anfuso, Cesarina Giallongo
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Uveal Neoplasms
Becaplermin
Vimentin
lcsh:Chemistry
STAT3
Uveal melanoma
Cancer-Associated Fibroblasts
Cell Movement
Tumor Microenvironment
Melanoma
lcsh:QH301-705.5
Spectroscopy
biology
Chemistry
General Medicine
PDGF-B
Neoplasm Proteins
Computer Science Applications
Gene Expression Regulation
Neoplastic
Interleukin 10
medicine.anatomical_structure
Matrix Metalloproteinase 9
Imatinib Mesylate
Pericyte
Platelet-derived growth factor receptor
Motility
Article
Retina
Catalysis
Receptor
Platelet-Derived Growth Factor beta
Transforming Growth Factor beta1
Inorganic Chemistry
Gentamicin protection assay
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Wound Healing
Tumor microenvironment
Organic Chemistry
medicine.disease
Coculture Techniques
Coculture
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Cancer research
Pericytes
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 15
International Journal of Molecular Sciences, Vol 21, Iss 5557, p 5557 (2020)
Popis: Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line. In our model system, HRPC were conditioned by co-culturing with 92.1UM for 6 days (cHRPC), in the presence or absence of imatinib, to block PDGF receptor-&beta
(PDGFR&beta
). The effects of the treatments were tested by wound healing assay, proliferation assay, RT-PCR, high-content screening, Western blot analysis, and invasion assay. Results showed profound changes in cHRPC shape, with increased proliferation and motility, reduction of NG2 and increase of TGF-&beta
1, &alpha
SMA, vimentin, and FSP-1 protein levels, modulation of PDGF isoform mRNA levels, phospho-PDGFR&beta
and PDGFR&beta
as well as phospho-STAT3 increases. A reduction of IL-1&beta
and IFN&gamma
and an increase in TNF&alpha
IL10, and TGF-&beta
1, CXCL11, CCL18, and VEGF mRNA in cHRPC were found. Imatinib was effective in preventing all the 92.1UM-induced changes. Moreover, cHRPC elicited a significant increase of 92.1UM cell invasion and active MMP9 protein levels. Our data suggest that retinal microvascular pericytes could promote 92.1UM growth through the acquisition of the CAF phenotype.
Databáze: OpenAIRE
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