Washington: A recent study has revealed that anti-melanoma drugs may induce a senescence-associated secretory profile (‘secretome’) that can promote metastasis and contribute to melanoma relapse.
Although, cellular senescence has been considered as a natural mechanism to combat uncontrolled cell growth or cancer, some cell types express a secretome during senescence.
This alters the tumour microenvironment and affects the cell`s response to chemotherapeutic drugs.
The study shows that depletion of the MITF transcription factor or exposure to anti-melanoma drugs activates the DNA damage response and triggers senescence.
Consequently, senescent melanoma cells express a PARP-1 and NF-kB—associated secretome, which contains high levels of the chemokine CCL2.
CCL2, in turn, leads to a loss of E-cadherin expression and an invasive phenotype.
In fact, culturing melanoma cells with exogenous CCL2 enhances their survival and invasiveness. This study suggests that blocking CCL2, or its upstream effectors may represent a novel therapeutic pathway.
"Our data disclose a part of the mechanisms contributory to failure of anti-melanoma chemotherapies and we gain valuable insight for the identification of new candidates, namely PARP-1, NF-kB or CCL2, for therapeutic intervention in view to overcome drug resistance," said Dr. Bertolotto.