Development of a Stromal Microenvironment Experimental Model Containing Proto-Myofibroblast Like Cells and Analysis of Its Crosstalk with Melanoma Cells: A New Tool to Potentiate and Stabilize Tumor Suppressor Phenotype of Dermal Myofibroblasts.
Actins
/ metabolism
Adult
Cell Communication
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Survival
/ drug effects
Cells, Cultured
Cellular Microenvironment
Culture Media, Conditioned
/ pharmacology
Cyclooxygenase 2
/ metabolism
Female
Humans
Melanoma
/ metabolism
Middle Aged
Myofibroblasts
/ cytology
Phenotype
Spheroids, Cellular
/ cytology
Tumor Microenvironment
Vimentin
/ metabolism
conditioned medium
melanoma
proto-myofibroblasts
stromal microenvironment
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
14 11 2019
14 11 2019
Historique:
received:
27
09
2019
revised:
08
11
2019
accepted:
12
11
2019
entrez:
20
11
2019
pubmed:
20
11
2019
medline:
23
7
2020
Statut:
epublish
Résumé
Melanoma is one of the most aggressive solid tumors and includes a stromal microenvironment that regulates cancer growth and progression. The components of stromal microenvironment such as fibroblasts, fibroblast aggregates and cancer-associated fibroblasts (CAFs) can differently influence the melanoma growth during its distinct stages. In this work, we have developed and studied a stromal microenvironment model, represented by fibroblasts, proto-myofibroblasts, myofibroblasts and aggregates of inactivated myofibroblasts, such as spheroids. In particular, we have generated proto-myofibroblasts from primary cutaneous myofibroblasts. The phenotype of proto-myofibroblasts is characterized by a dramatic reduction of α-smooth muscle actin (α-SMA) and cyclooxygenase-2 (COX-2) protein levels, as well as an enhancement of cell viability and migratory capability compared with myofibroblasts. Furthermore, proto-myofibroblasts display the mesenchymal marker vimentin and less developed stress fibers, with respect to myofibroblasts. The analysis of crosstalk between the stromal microenvironment and A375 or A2058 melanoma cells has shown that the conditioned medium of proto-myofibroblasts is cytotoxic, mainly for A2058 cells, and dramatically reduces the migratory capability of both cell lines compared with the melanoma-control conditioned medium. An array analysis of proto-myofibroblast and melanoma cell-conditioned media suggests that lower levels of some cytokines and growth factors in the conditioned medium of proto-myofibroblasts could be associated with their anti-tumor activity. Conversely, the conditioned media of melanoma cells do not influence the cell viability, outgrowth, and migration of proto-myofibroblasts from spheroids. Interestingly, the conditioned medium of proto-myofibroblasts does not alter the cell viability of both BJ-5ta fibroblast cells and myofibroblasts. Hence, proto-myofibroblasts could be useful in the study of new therapeutic strategies targeting melanoma.
Identifiants
pubmed: 31739477
pii: cells8111435
doi: 10.3390/cells8111435
pmc: PMC6912587
pii:
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
Culture Media, Conditioned
0
VIM protein, human
0
Vimentin
0
Cyclooxygenase 2
EC 1.14.99.1
PTGS2 protein, human
EC 1.14.99.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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