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Abstract
Malignant melanoma (MM) represents the most aggressive and deadly form of skin cancer relating to only about 5 % of all skin cancers, but accounting for about 65 % of skin cancer deaths. Current therapies mainly focus on targeting melanoma cells directly; however, other cell types, including cancer-associated -fibroblasts (CAFs), forming the tumour microenvironment (TME) support cancer progression. Moreover, they also play an important role in tumour relapse and therapeutic resistance. Thus, targeting CAFs has recently entered the limelight of cancer therapy. However, molecular mechanisms underlying the interplay between melanoma cells and CAFs at the site of the primary tumour and especially in the TME of distant metastases remain largely elusive. Therefore, in order to identify novel players in melanoma progression, I aimed at defining and analysing alterations in the genetic programs of CAFs during various phases of MM. To achieve this, I employed an improved mouse model of MM development, progression and metastasis. In a first step, I investigated the effect of CAF- specific loss of PDPN on primary tumour growth. In a second, more comprehensive approach, cells from the tumour stroma at primary tumour and lung metastatic sites were isolated applying an optimised protocol for tissue dissociation at low temperatures and isolation of viable single cells, followed by scRNA sequencing.
Document type: | Dissertation |
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Supervisor: | Angel, Prof. Dr. Peter |
Place of Publication: | Heidelberg |
Date of thesis defense: | 27 April 2023 |
Date Deposited: | 25 Jul 2023 07:27 |
Date: | 2024 |
Faculties / Institutes: | The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences |
DDC-classification: | 570 Life sciences |