Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis, and reduces survival in a spontaneous xenograft model of human breast cancer

Autor: Stepan Nersisyan, Sabrina Arnold, Alexander G. Tonevitsky, Christine Stürken, Susanne Lezius, Udo Schumacher, Timur R. Samatov, D. V. Maltseva, Jan Kortland, Daniel Wicklein, Karin Milde-Langosch
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cancer Research and Clinical Oncology. 148:1525-1542
ISSN: 1432-1335
0171-5216
Popis: PurposeThe transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis. As so far, no in vivo data are available, this study was designed to elucidate the role of Fra-2 expression in a spontaneous breast cancer metastasis xenograft model.MethodsThe effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA MB231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin-deficient scid mice.ResultsFra-2 overexpression leads to a significantly shorter overall survival and a higher amount of spontaneous lung metastases not only in scid mice, but also in E- and P-deficient mice, indicating that it regulates not only selectin ligands, but also selectin-independent adhesion processes.ConclusionThus, Fra-2 expression influences the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells in a breast cancer xenograft model.
Databáze: OpenAIRE
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