Transfer von Pluripotenzfaktoren maligner Stro-1-positiver und Stro-1 negativer Zellen auf tumorfremde somatische Zellen

Transfer von Pluripotenzfaktoren maligner Stro-1-positiver und Stro-1 negativer Zellen auf tumorfremde somatische Zellen

Study on the transfer of pluripotency factors from malignant STRO-1+ and STRO-1− cells to non-tumorous somatic cells

Julia Walter

Doctoral thesis

Date of Examination: 2016-10-25

Date of issue: 2016-10-18

Advisor: Wiese, Karl Günter Prof. Dr. Dr.

Referee: Miosge, Nicolai Prof. Dr.

Referee: Oppermann, Martin Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-002B-7C2D-1

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Abstract

English

Despite the fact that a tremendous research effort has been made, the formation, dissemination and the progress of metastatic spread of a tumour disease is not yet entirely understood. However, it is known that so-called tumour stem cells, which share many similarities with true stem cells, play a vital role regarding tumour progression, malignity and the resistance to chemotherapy treatment of carcinosis. In this context, we identified in an ectodermal tumour cell line (Hep2, laryngeal carcinoma cells) and in a mesenchymal cell line (SAOS, osteosarcoma cells) a subpopulation, which expresses the stem cell marker STRO-1. Positive and negative STRO-1 cells were further studied with regard to the transfer of pluripotency factors, which are known to cause induced pluripotency in cells. Both cell lines express the pluripotency factors Oct4, c-myc, Sox2 and Nanog. In co-cultural trials, we were able to detect that all osteosarcoma cells (STRO-1+ and STRO-1−) had transferred the four pluripotency factors to somatic cells, in contrast to Hep2 cells, where only a transfer of Oct4 and Nanog was detected. The various intercellular junctions found in the co-culture led to the assumption of a transfer of these factors by means of nanotubes. A transfer of Oct4 by means of exosomes could be excluded. In summary, it was shown that both tumour cell lines were able to transfer pluripotency factors to somatic cells and consequently influence their cellular behaviour. However, it still needs to be fully clarified, which cell population is responsible for the transfer of these factors and how they eventually affect the somatic cells. Nevertheless, the results could be considered a point of reference regarding a mechanism for the expansion of a tumour cell subpopulation, which causes redifferentiation leading to a more aggressive tumour spread.

Keywords: Stro-1; Oct4; pluripotency; cancer; SAOS; Hep2

Schlagwörter: Stro-1; Oct4; Pluripotenz; Krebs; SAOS; Hep2