Unknown,Transcriptomics,Genomics,Proteomics

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Molecular profiling of immune activation associated with regression of melanoma metastases induced by diphencyprone

ABSTRACT: The purpose of this study was to treat cutaneous melanoma metastases with topical DPCP, and then to comprehensively study the induced immune responses associated with tumor regression. Six melanoma patients were sensitized to 0.4% DPCP on one of their cutaneous metastases and their right upper arm, as well on their left lower arm. Two weeks later, effective sensitization was confirmed by noting induration at the application sites, and then challenge applications were applied to the subjectâs cutaneous metastases. Also at this visit, one 0.2 mL application of 0.4% DPCP was applied to one area of non-melanoma skin, and another 0.2 mL application of 0.04% DPCP was applied to a different area of non-melanoma skin. For all patients, one of the inflamed non-melanoma sites challenged with DPCP was biopsied 3 days later. All patients continued to receive their standard oncologic follow-up and monitoring visits.

ORGANISM(S): Homo sapiens

SUBMITTER: Mayte Suarez-Farinas

PROVIDER: E-GEOD-82105 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Brain metastases of melanoma are associated with therapy resistance and poor prognosis. It is not fully understood whether and how the selection of cells capable of metastasizing into the brain is accompanied by the establishment of specific features. For the investigation of these questions, we made use of previously described xenograft mouse models for primary human melanoma cells distinguishing cutaneous from cerebellar metastases from the same genetic background. Previous experiments suggested that cultured cells derived from these xenografts still maintain properties characteristic for the microenvironment of the originating metastases. Such corresponding pairs of metastatic cells were obtained from four individual donors, resulting in eight cell-lines presently investigated with regard to molecular properties characteristic for metastasis. Label free proteome profiling revealed significant alterations when comparing corresponding pairs of cutaneous and cerebellar metastases from the same donor. Molecules previously associated with metastasis such as cell adhesion molecules, immune regulators, epithelial mesenchymal transition markers, stem cell markers, redox regulators and cytokines were found differently expressed. This was also observed with regard to eicosanoids considered relevant for metastasis such as PGE2 and 12-HETE. However, no commonalities in the molecular characteristics of cerebellar metastases were identified in all four donors. Multiparametric morphological analysis of cells also revealed alterations associated with the kind of metastases, while lacking uniformity. In conclusion, here we describe that xenografted melanoma cells derived from two different microenvironments, i.e. cutaneous and cerebellar metastases, display significant alterations in the expression of molecules associated with metastastic properties. The observed lack of uniformity suggests that metastatic cells may find individual strategies to adapt to their microenvironmental challenges accompanied by the establishment of individual cell characteristics.

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Molecular profiling of immune activation associated with regression of melanoma metastases induced by diphencyprone

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