Lene Uhrbom – Investigations of local peripheral glioblastoma cells

Glioblastoma is an aggressive primary brain cancer for which there is no effective treatment. Knowledge about glioblastoma is largely based on studies of bulk tumours, i.e, the part that is visible through magnetic resonance imaging (MRI) and that is surgically resected. There are few studies of the locally invasive cancer cells that remain in the brain and subsequently cause recurrence. These edge glioblastoma cells are the focus of our studies, which aim to clarify their biology, identify their vulnerabilities, and develop new therapies.

Glioblastoma is an aggressive primary brain cancer that mainly affects adults. At the time of diagnosis, a large number of cancer cells have already spread beyond the part of the tumour that is visible by MRI, which means that the patient can never be cured by surgery.

For over two decades, the standard treatment has consisted of maximal-safe surgical removal of tumour tissue, followed by concomitant radiation and chemotherapy to target the invasive cancer cells. Despite this, virtually all patients suffer an incurable recurrence close to the resection cavity of the primary tumour.

Patient samples, disease models and biology

In order to study the glioblastoma cells that must be neutralized if glioblastoma is to be cured, we collect patient samples. During surgery, multiple samples are collected beyond the visible tumour (as determined by MRI) and from the bulk tumour of each patient. These are used for analyses and to establish cell cultures. Cell cultures are important disease models for functional analyses and screening of edge glioblastoma cells.

Schematic drawing of how patient samples are collected and analysed i different ways.

Multiple samples are collected during surgery, from the bulk tumour and the periphery, of each patient. From the samples glioblastoma cells are cultivated and studied using functional, phenotypic and molecular analyses to determine their function and regulation. Image: Lene Uhrbom

Our studies include characterizing the functional, phenotypic and molecular intra- and intertumoral heterogeneity of edge glioblastoma cells and understanding their regulation and function in relation to their matched bulk tumour cells. We also aim to identify mechanisms of therapy escape and new therapeutic targets.

Another important goal is to make the established disease models – patient-derived cell cultures and orthotopic mouse models that represent the clinical landscape of the edge glioblastoma cells – available to other researchers to contribute to faster advances in the glioblastoma field.

Microscope image of cells showing differences between bulk tumour cells and edge cells

Glioblastoma cells (in pink) in tumour samples of the bulk tumour (left) and periphery (right) of the same patient. Immunostainings of two different proteins detected in pink (tumour cell-specific) and green (tumour cells and one type of glia cell). Blue shows the nuclei of all cells in the tissue sample. Image: Veera Jokinen.

Microscope images showning different numbers and shapes of cultivated cells from the bulk tumour and from the tumour edge.

Cultured glioblastoma cells from a bulk tumour sample (left) and two different peripheral samples (middle and right) of the same patient. Image: Veera Jokinen.