The role of tumour-initiating cells in breast cancer and malignant melanoma

Tumors are heterogeneous and contain cell populations that differ with respect to growth kinetics, metastatic potential and response to therapies. The cancer stem cell hypothesis provides an attractive cellular explanation to account this heterogeneity. According to this hypothesis, tumours are hierarchically organized, and at the top of the hierarchy lie tumour-initiating cells (TIC) often called "cancer stem cells" (CSC). CSC refer to a rare subpopulation of tumour cells with stem cell properties (i.e. ability to self-renew and differentiate) that are key cells in tumour initiation and progression (Reya et al. 2001). Moreover, TIC seem to be resistant to conventional therapies, thus eradication of such stem-like tumour-initiating cells should be of crucial importance for treating cancer patients.

The CSC hypothesis has recently received considerable attention, and several groups at the Institute for Cancer Research, Norwegian Radium Hospital and University of Oslo participate in The Cancer Stem Cell Innovation Center (CAST) supported by the Research Council of Norway. The focus of CAST is to investigate stem cell-like tumour-initiating cells with the aim to develop novel anticancer therapies.

Our group is a partner in CAST and we focus on studies of the TIC subpopulations in two types of solid tumours - breast cancer and malignant melanoma. We aim to reveal the role of such cells in the progression of these tumors, and, furthermore, to reveal targets for TIC therapy. The studies involve isolation and molecular and functional characterization of candidate TIC subpopulations in vitro and investigation of their tumorigenic and metastatic potential in vivo.

In the breast cancer subproject we utilize two orthotopically growing xenograft models representing basal-like and luminal A subtypes of the disease. We are investigating:

Functional differences between candidate TIC subpopulations, as defined by expression of putative stem cell related cell surface antigens, and the residual tumour cell populations.
Interactions between the TIC and the microenvironment niche by utilizing 3D organotypic assays. It is well known that the microenvironment, i.e the "niche" in where the stem cells reside, is of great importance for keeping "stemcellness", therefore, the studies on TIC and microenvironment interactions is of great interest trying to understand TIC. For more information contact Kristin Andersen or Geir Olav Hjortland.

In the melanoma project, we utilize lymph node biopsies from metastatic melanoma patients and from-them-established melanoma models in vitro and in vivo, and investigate:

The significance of the stem cell characteristics for melanoma aggressiveness.
The expression of the stem cell-related properties and parallelly evaluate the invasiveness and malignancy of the melanoma cells isolated from patient biopsies, cultures in vitro, xenografts and experimental metastases. For more information contact Lina Prasmickaite.

Reya, T., et al. (2001). "Stem cells, cancer, and cancer stem cells." Nature 414(6859): 105-11.