Tumour Biology and Molecular Markers GroupResearch Team Leader Katarzyna Lisowska, Ph. D., Dr. Sci.

MAIN RESEARCH TOPICS

Molecular markers in cancer

It is generally accepted that greater improvement in cancer therapy would be possible thanks to earlier diagnosis and individualized treatment. To help implement these ideas in the clinical practice, studies are underway in the search for new molecular markers of diagnostic, prognostic and predictive values.

Our projects start with DNA microarray-based high-throughput analyses. Further on they focus on more detailed characteristics of selected potential markers. We study the biological role of these genes/proteins and correlation of their expression levels with the occurrence and clinical course of the disease. The latter studies are done using clinical material.

Our projects concern breast, ovarian, and prostate cancer, as well as melanoma. We are also particularly interested in the studies of the role of BRCA1 gene mutation in the clinical course of the cancers involved. Our further interests concern the role of hypoxia in the context of cancer development and treatment, as well as the function of cytoprotective and antiapoptotic proteins from the HSP family.

Hypoxia in cancer

One of the most important features of tumor microenvironment causing adverse effect on patient prognosis is low oxygen tension within tumor mass. Not only does hypoxia reduce the effectiveness of standard therapies, but it also induces aggressive phenotype of the tumor cells. Better understanding of hypoxia role in tumor progression may thus contribute to improvements in cancer prognostication and treatment.

The main aim of the project is to find novel cancer markers and therapeutic targets among genes/proteins responsive to hypoxia. (more)

The first project concerned identification of hypoxia-responsive genes in melanoma cells. Using Affymetrix oligonucleotide microarray we have identified hypoxic signature in murine melanoma B16-F10 cells in vitro (Olbryt et al., Gene Expr., 2006, 13:191-203). Twenty two of the selected 430 hypoxia-responsive genes were verified in vivo in B16-F10 tumors, as well as in human melanoma cell lines in vitro. We identified three novel hypoxia-responsive genes in human and murine melanoma cells. These genes, MXI1, FN1, NME1 , are potential molecular regulators of aggressive phenotype of melanoma cells in the hypoxic microenvironment (Melanoma Res., 2011, 21:417-25). The aforementioned results are the mainframe of Magdalena Olbryt's Ph.D. thesis (“Gene expression profile induced by hypoxia in murine melanoma cells B16-F10”).

We have extended the project to ovarian and prostate cancers. The main aim of the project was to delineate the similarities and differences in gene expression between tumor cells exposed to two main types of tumor hypoxia: chronic (diffusion-limited hypoxia) and cycling ( perfusion-limited hypoxia/intermittent hypoxia). The first type appears in the tumor as a result of increased distances between proliferating cells and blood vessels. The second type is characterized by fluctuations of oxygen tension and is caused by instabilities in microregional blood flow, as well as vessel remodeling during angiogenesis. Both types induce rise of aggressive phenotypes of tumor cells and negatively influence the effectiveness of standard therapies. However, recent data indicate that the cycling hypoxia may have even more profound effect on tumor progression than the chronic one. Identification of genes/proteins specifically regulated by cycling hypoxia would enable not only to monitor tumor areas affected by it but also understand better the role of cycling hypoxia in tumor growth and dissemination. The far-reaching aim of our study is to identify the putative prognostic and predictive markers among hypoxia-responsive proteins and correlate their expression with patient survival.