Melanoma skin cancer has been increasing over the last 50 years, now representing 3% of total tumours. Despite the new immune-modulating therapies, the prognosis is still unfavorable, so further therapeutic options are needed. The goal of the project is to establish advanced 3D human melanoma models, as useful and more predicting tools for preclinical studies. We established two different 3D human melanoma models: i) A commercially available model (Mattek, USA), able to recapitulate the main melanoma progression stages occurring in vivo (the radial, vertical, and metastatic growth phases), containing A375 melanoma cells, was used to test innovative drug-loaded nanoparticles (HNE-NCs). We performed two diverse treatments, one mimicking the parenteral, and the other the topical administration. IHC analysis were performed to examine proliferation index (Ki67) and tumor invasivity (S100). ii) A home-made model, where primary normal human Keratinocytes (KCs) were stratified onto a collagen based dermis enriched with primary normal human fibroblasts (HDFs). We assessed this model not only with commercially available A375 cells, but also with two patients derived primary melanoma cells. In vitro 3D tissues were morphologically characterized by H&E analysis; an IHC analysis (Ki67 and S100) was also made. We demonstrated the anti-proliferative effect of the -loaded nanoparticles (HNE-NCs) in the commercial melanoma model, as demonstrated by H/E, Ki67 and S100 markers. Interestingly, we also obtained encouraging results with the topic administration. Moreover the morphology and proliferation/invasion markers expression of the home-made 3D model correlate with the diverse malignant features of the patients derived primary melanoma cells. Our engineered 3D human skin melanoma models can be suitable for cancer progression studies, targets and drugs discovery and development. The use of patients derived cells will allow achieving personalized cancer treatments. Further addiction of immune cells inside the models will pave the way towards the study of immune-modulating drugs as well.
3D advanced human melanoma models
DIANZANI, Chiara;CAVALLI, Roberta;CASSONI, Paola;ANNARATONE, LAURA;RIBERO, Simone;RUSSO, ROSALIA;SENETTA, REBECCA;DAGA, MARTINA;BARRERA, Giuseppina;PIZZIMENTI, Stefania
2017-01-01
Abstract
Melanoma skin cancer has been increasing over the last 50 years, now representing 3% of total tumours. Despite the new immune-modulating therapies, the prognosis is still unfavorable, so further therapeutic options are needed. The goal of the project is to establish advanced 3D human melanoma models, as useful and more predicting tools for preclinical studies. We established two different 3D human melanoma models: i) A commercially available model (Mattek, USA), able to recapitulate the main melanoma progression stages occurring in vivo (the radial, vertical, and metastatic growth phases), containing A375 melanoma cells, was used to test innovative drug-loaded nanoparticles (HNE-NCs). We performed two diverse treatments, one mimicking the parenteral, and the other the topical administration. IHC analysis were performed to examine proliferation index (Ki67) and tumor invasivity (S100). ii) A home-made model, where primary normal human Keratinocytes (KCs) were stratified onto a collagen based dermis enriched with primary normal human fibroblasts (HDFs). We assessed this model not only with commercially available A375 cells, but also with two patients derived primary melanoma cells. In vitro 3D tissues were morphologically characterized by H&E analysis; an IHC analysis (Ki67 and S100) was also made. We demonstrated the anti-proliferative effect of the -loaded nanoparticles (HNE-NCs) in the commercial melanoma model, as demonstrated by H/E, Ki67 and S100 markers. Interestingly, we also obtained encouraging results with the topic administration. Moreover the morphology and proliferation/invasion markers expression of the home-made 3D model correlate with the diverse malignant features of the patients derived primary melanoma cells. Our engineered 3D human skin melanoma models can be suitable for cancer progression studies, targets and drugs discovery and development. The use of patients derived cells will allow achieving personalized cancer treatments. Further addiction of immune cells inside the models will pave the way towards the study of immune-modulating drugs as well.
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