Breast cancer consists of a multitude of different diseases with varying behaviours and it is critical to identify subgroups with similar tumour biological properties as well as define groups that will respond to specific treatments.
In the quest to understand this challenging disease we focus our study on the complex interactions between tumour microenvironment (TME) and breast cancer stem cells (BCSC). Cancer stem cells has been described as the major reason for why many solid tumors relapse and progress after treatment due to their ability to self-renew and resistance to conventional therapy.
Within the project we have pinpointed several components from the microenvironment affecting the BCSC pool. One of our findings is that subtypes of breast cancers has a contrasting response to low oxygen. Oxygen levels influence the differentiation state of the cells and alter cell secretion. Our aim is to find details in the mechanisms behind this contrasting behaviour as well as identify key regulators mediating the obvious increase of cancer stem cells in some tumours during hypoxia. Ultimately we will identify novel inhibitors that block this process.
To further understand the interactions between TME and BCSC we have developed a new model system, patient derived scaffolds (PDS), consisting of cell free patient extracellular matrix and conventional breast cancer cell lines. In this model we have identified novel information about how the TME affects cancer cell transcriptomic profiles and secretion behaviors. We have found that each individual patient sample induce a unique shift in cancer cell processes such as epithelial-mesenchymal transition (EMT), differentiation and proliferation that can be correlated back to clinical observations. We now develop this system further to become a drug testing platform bridging between in vitro and in vivo drug testing to improve future clinical trials and enable a reduction in animal use.
Another main goal within the research group is to develop novel cancer therapies by blocking breast cancer stem cell progression and dedifferentiation to improve patient outcome.
We provide an integrated approach for breast cancer research by combining the analysis of clinical observations with cell and molecular techniques in the laboratory. We also construct and analyse large sets of primary tumour materials in tissue microarrays (TMAs) and scaffold cultivations, linked to clinical data bases.
Current group members
Göran Landberg, MD, PhD, Professor
Elena Garre, Researcher
Sara Rhost, Researcher
André Holdfeldt, Associate Researcher
Simona Salerno, Postdoc
Anna Gustafsson, PhD student
Karoline Berger, PhD student
Nushin Mirzaei, MD, PhD student
Jennifer Rosendahl, PhD student
Pernilla Gregersson, Technician, Lab manager
Recent selected publications
- Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre-invasive phenomena that is prognostic in invasion.
Shaker Hm Bundred NJ, Landberg G, Pritchard SA, Albadry H, Nicholson SL, Harries LJ, Heah JYE, Castle J, Kirwan CC. Cancer Med 9 (5); 2020, 1768-1778.
- Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment.
Landberg G, Fitzpatrick P, Isakson P, Jonasson E, Karlsson J, Larsson E, Svanström A, Rafnsdottir S, Persson E, Gustafsson A, Andersson D, Rosendahl J, Petronis S, Ranji P, Gregersson P, Magnusson Y, Håkansson J, Ståhlberg A. Biomaterials; 2020, 235.
- Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells.
Jonasson E, Ghannoum S, Persson E, Karlsson J, Kroneis T, Larsson E, Landberg G, Ståhlberg A. Front Genet. 2019, May 22
- Hypoxia-induced secretion stimulates breast cancer stem cell regulatory signalling pathways.
Jacobsson H, Harrison H, Hughes É, Persson E, Rhost S, Fitzpatrick P, Gustafsson A, Andersson D, Gregersson P, Magnusson Y, Ståhlberg A, Landberg G. Mol Oncol. 2019, Aug 13
- Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion.
Rhost S, Hughes É, Harrison H, Rafnsdottir S, Jacobsson H, Gregersson P, Magnusson Y, Fitzpatrick P, Andersson D, Berger K, Ståhlberg A, Landberg G. Breast Cancer Res. 2018 Nov 20
- Cellular organization and molecular differentiation model of breast cancer-associated fibroblasts.
Busch S, Andersson D, Bom E, Walsh C, Ståhlberg A, Landberg G. Mol Cancer. 2017 Apr 3
- High expression of stromal PDGFRβ is associated with reduced benefit of tamoxifen in breast cancer.
Paulsson J, Rydén L, Strell C, Frings O, Tobin NP, Fornander T, Bergh J, Landberg G, Stål O, Östman A. J Pathol Clin Res. 2016 Sep 14
- Robotic mammosphere assay for high-throughput screening in triple-negative breast cancer.
Fitzpatrick PA, Akrap N, Söderberg EMV, Harrison H, Thomson GJ, Landberg G. SLAS Discov 22, 827-836, 2017.
- Identification of distinct breast cancer stem cell populations based on single-cell analyses of functionally enriched stem and progenitor pools.
Akrap N, Andersson D, Bom E, Gregersson P, Ståhlberg A, Landberg G. Stem Cell Reports 6, 121-136, 2015.
- Loss of TGFbeta receptor type 2 expression impairs estrogen response and confers tamoxifen resistance.
Busch S, Sims AH, Stål O, Fernö M, Landberg G. Cancer Res, 75, 1457-1469, 2015.
More group Göran Landberg publications on PubMed