Breast cancer metastasis

Regional lymph node metastasis in breast cancer
For more than 80% of breast cancer patients with distant metastasis, the cancer cells 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 rarely taken into account in breast cancer metastasis studies.

In Norway, about 13% of breast cancer patients are diagnosed with metastatic spread to regional lymph nodes. Current clinical practice focuses mainly on the presence and size of metastatic lesions in the lymph nodes, and there is substantial variation in how positive results are interpreted across hospitals in Norway.

Foto: Jørn Berger-Nyvoll/UiT

Research strategy and methods
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

Feith, M., Sajib, S.D., Myrann, A.G., Høgset, A., Garrido, P., Martinez, A., Knutsen, E., Sandvig, K., Skotland, T., Mælandsmo, G.M. & Iversen, T.-G. (2025)

Induction of Cell Death by Combined Treatment with Photosensitizer-Chitosan Nanoparticles and the Ferroptosis Inducer RSL3 in Breast Cancer Cell Lines

Advanced NanoBiomed Research, Volume 5. 2025

DOI 10.1002/anbr.202400208

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, Volume 14. 2022

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., Volume 12. 2022

DOI 10.3389/fonc.2022.868868

Nyhetssaker

Foto: Jørn Berger-Nyvoll/UiT

Nordnorsk debatt: Hva skal vi med kreftforskning?

«Treningsfysiolog Anders Haakenstad kommer med flere hårreisende usannheter i podcasten «Wolfgang Wee Uncut». Flere ganger påstår han at kreftforskningen er uredelig og at helsevesenet og andre aktører styres av økonomiske interesser, mens han selv selger sine råd og tjenester.»

Foto: Gordon Research Conference

Gordon Research Conference 2024

Discovery and Translation in Proteoglycan Research. Andover, NH, United States.

Title of talk: Proteoglycans as important singling molecules in the crosstalk between tumor infiltrating immune cells and cancer cells.

Foto: Oddleif Larsen/UiT

Får 8 millioner fra Kreftforeningen

Nylig fikk førsteamanuensis ved Institutt for medisinsk biologi på det Helsefaglige fakultet, Erik Knutsen, en telefonsamtale utenom det vanlige. Han er en av fem unge forskere som har fått innvilget søknad fra Kreftforeningen