Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells
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Data
2020-08-29
Autores
Pessotti, Dayelle 
Zelanis, André
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The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the
phenotype of tumoral cells and have significant implications in cancer development and progression. In this
study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human
dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In
addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own
conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results
revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators.
The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related
to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the
conditioned medium derived from ‘primed’ stromal cells (melanoma-stimulated fibroblasts) was more effective
in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from nonstimulated
fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment
and enable tumoral cells to succeed in the process of melanoma progression and metastasis.
Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a
highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from
stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression
and metastasis.