Breast cancer metastasis

For more than 80% of breast cancer patients with distant metastasis, the cancer cells did initially travel via the regional lymph nodes before entering into systemic circulation. However, the fact that breast cancer mainly spreads through the lymph nodes and do not enter systemic circulation by a direct extravasation into the blood flow at the primary tumor site is seldomly taken into account in breast cancer metastasis studies. In Norway, ~13% of breast cancer patients are diagnosed with metastatic spread to the regional lymph nodes. The current clinical method for diagnosis only examines the presence and sizes of the metastatic lesions in the lymph nodes and there is a large variability in the interpretation of positive results between hospitals in Norway

Foto: Jørn Berger-Nyvoll/UiT

In this project, we hypothesize that cancer cells present in the lymph nodes will have a specific protein and transcriptome profile that reflects how the cancer cells have been stimulated by the lymph node microenvironment, and that these identified changes will be associated with a change in their potential for further metastatic spread. To examine this, we are examining the transcriptional changes during the metastatic cascade in breast cancer patients by single cell sequencing and will correlate our data towards the number of circulating tumor cells (CTCs) present in the blood. We further hypothesize that an epithelial-mesenchymal transition (EMT) or a stem cell phenotype can be induced by the lymph node microenvironment, and that a blocking of this interaction can be for prevention of metastasis. Here, we are using an in-house EMT scoring algorithm to identify cancer cells with specific transcriptional signatures reflecting their phenotypes. By combining data on CTCs, EMT scoring, and gene and protein expression signatures, we anticipate that we can deduct a high-risk transcriptome profile with an innovative potential to be used in the clinic for guiding treatment choice and prognostic evaluation.

Foto: Jørn Berger-Nyvoll/UiT

The research project has strong local, national, and international collaborators, including Prof. Elin S. Mortensen (local, UNN), Dr. Vegard Heimly Brun (local, UNN), Dr. Åse Florholmen-Kjær (local, UNN), Dr. Bård Ove Karlsen (local, Nordland Hospital), Dr. Xavier Tekpli (National, OUH), Dr. Marieke Kuijjer (National, UiO), Prof. Gunhild Mælandsmo (National, OUH), and Prof. Calin (International, MD Anderson Cancer Center).

Publications

	Knutsen, E., Sajib, S.D., Fiskaa, T., Lorens, J., Gudjonsson, T., Mælandsmo, G.M., Johansen, S.D., Seternes., O.M. & Perander, M. (2023) Identification of a core EMT signature that separates basal-like breast cancers into partial- and post-EMT subtypes Frontiers, Volume 13 - 2023 DOI 10.3389/fonc.2023.1249895
	Karagiorgou, Z., Founta, P.N, Manou, D., Knutsen, E., & Theocharis, A.D. (2022) Proteoglycans Determine the Dynamic Landscape of EMT and Cancer Cell Stemness. Cancers 2022, 14, 5328. DOI 10.3390/cancers14215328
	Tellez-Gabriel, M.,Tekpli, X., Reine, T.M., Hegge,B., Nielsen, S.R., Chen, M., Moi, L., Normann, L.S., Busund, L.T.R., Calin, G.A., Mælandsmo, G.M., Perander, M., Theocharis, A.D., Kolset, S.O. & Knutsen, E. (2022) Serglycin Is Involved in TGF-β Induced Epithelial-Mesenchymal Transition and Is Highly Expressed by Immune Cells in Breast Cancer Tissue Front. Oncol. 12:868868 DOI 10.3389/fonc.2022.868868