New analysis methodology may revolutionize breast cancer therapy
Stroma cells are derived from connective tissue and may critically influence tumour growth. This knowledge is not new. However, bioanalyst Christopher Gerner and an interdisciplinary team from the University of Vienna and the Medical University of Vienna have developed a novel methodology for investigation. Using modern mass spectrometry, tumour-promoting activities from breast fibroblasts were directly determined from needle biopsy samples. Recently this experimental break-through is published in the renowned Journal of Proteome Research.
The potential contribution of stroma cells to tumour growth has been widely recognised. It is not easy to understand whether a diseased stroma state supports tumour initiation or, alternatively, tumour- stroma cells are responsible for the formation of such diseased stroma. “We successfully identified relevant players as such and analysed these molecules out of human tissue samples for the very first time”, says Christopher Gerner, head of the Department of Analytical Chemistry of the University of Vienna. Together with Georg Pfeiler from the Department of Obstetrics and Gynecology of the Medical University of Vienna and an interdisciplinary research team, he has developed the new analysis methodology.
Experimental determination of undesirable tumour promotion by stroma cells
Tissue is made of various cell types, which fulfil different biological tasks. Main components of breast tissue are epithelial cells and fibroblasts. In case of breast cancer, the epithelial cell may transform while the fibroblasts, remaining genetically unaltered, may change their activation state. The typical activity of cancer associated fibroblasts (CAFs) is similar to wound healing activities. The secreted growth- and survival factors, biologically active at extremely low concentrations, are not only supporting wound healing, but may as well be exploited in case of cancer for further promotion of the disease. The significance of such cell activities has been fully acknowledged only during the last few years, the current study also presents a relevant in vitro model for more detailed investigations.
Innovative assay based on mass spectrometric analyses of needle biopsies
It was a real analytical challenge to identify the most relevant molecular players out of tissue homogenates which consist of a complex mixture of different kinds of cells together with countless blood constituents. By the use of modern mass spectrometry several thousand distinct proteins were identified in a first step. Referring to the in vitro model systems mentioned above, it was finally possible to investigate the functional cell state of fibroblasts out of tissue homogenates. This successfully proved that in case of cancer, the fibroblasts display a strong wound healing activity and thus directly promote tumour growth. “This was only possible due to the modern instrumentation I got together with the chair in Bioanalysis”, remarks Christopher Gerner referring to the top instruments in the Mass Spectrometry Center of the University of Vienna.
Breast Cancer Treatment
There are two major goals of breast cancer treatment:
1) To rid the body of the cancer as completely as possible
2) To prevent cancer from returning
How Is the Type of Breast Cancer Treatment Determined?
The type of breast cancer treatment recommended for you will depend on the size of your tumor, the extent of disease in your lymph nodes and/or throughout your body (the stage), and the overexpression of the HER2 protein and/or endocrine receptors (estrogen and progesterone). Age, menstrual status, underlying health issues, and personal preferences also play a role in this decision-making process.
What Are the Types of Breast Cancer Treatment?
Breast cancer treatments are local or systemic.
Local treatments are used to remove or destroy the disease within the breast and surrounding regions, such as lymph nodes. These include:
Surgery, either mastectomy or lumpectomy - also called breast-conserving therapy. There are different types of mastectomies and lumpectomies.
Radiation therapy
Systemic treatments are used to destroy or control cancer cells all over the body and include:
Chemotherapy uses drugs to kill cancer cells. Side effects can include nausea, hair loss, early menopause, hot flashes, fatigue, and temporarily lowered blood counts.
Hormone therapy (endocrine therapy) such as tamoxifen in premenopausal and postmenopausal women and the aromatase inhibitors Arimidex, Aromasin, and Femara in postmenopausal women. Hormone therapy uses drugs to prevent hormones, especially estrogen, from promoting the growth of breast cancer cells. Side effects can include hot flashes and vaginal dryness.
Biological therapy such as Herceptin, Perjeta, or Tykerb, which work by using the body’s immune system to destroy cancer cells. These drugs target breast cancer cells that have high levels of a protein called HER2.
Systemic therapy may be given after (adjuvant therapy) or before (neoadjuvant therapy) local treatment. Adjuvant therapy is used after local treatments to kill any cancer cells that may remain in the body but are undetectable. It is also used for people with advanced disease.
You may have just one form of breast cancer treatment or a combination of treatments, depending on your needs.
Novel approaches for breast cancer therapy
The results of the current study may have several consequences. Based on needle biopsies, it is now possible to assess functional states of stroma cells. “It is therefore feasible for us to determine to which extent such activities are present and relevant in individual patient samples. This is a first step which may allow us to plan pharmacological interference. However, these are future hopes when referring to clinical practice”, says Georg Pfeiler of the Medical University of Vienna. “For that aim we are currently developing an assay using blood serum only”, adds Christopher Gerner. Furthermore, it is now possible to use the in vitro model system to test drug candidates interfering with these undesirable cell activities in a targeted fashion. Clinical application of such an additional therapeutic strategy could substantially improve current therapies with respect to life quality parameters and prognosis.
Currently a team consisting of several PhD-students are working on the realisation of these research projects. Indeed this may typically represent a cross-over project involving experts from bioanalytics, medicine and pharmacology.
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Publication in Journal of Proteome Research (Special Issue: Proteomics of Human Diseases: Pathogenesis, Diagnosis, Prognosis, and Treatment): Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts. Michael Groessl, Astrid Slany, Andrea Bileck, Kerstin Gloessmann, Dominique Kreutz, Walter Jaeger, Georg Pfeiler, Christopher Gerner. September 2014. DOI: 10.1021/pr500727h http://pubs.acs.org/doi/abs/10.1021/pr500727h
The University of Vienna, founded in 1365, is one of the oldest and largest universities in Europe. About 9,500 employees, 6,700 of who are academic employees, work at 15 faculties and four centres. This makes the University of Vienna Austria’s largest research and education institution. About 92,000 national and international students are currently enrolled at the University of Vienna. With more than 180 degree programmes, the University offers the most diverse range of studies in Austria. The University of Vienna is also a major provider of continuing education. In 2015, the Alma Mater Rudolphina Vindobonensis celebrates its 650th Anniversary. http://www.univie.ac.at
The Medical University of Vienna (abbreviation: MedUni Vienna) is one of Europe’s medical training and research facilities with the greatest history and tradition. Counting almost 7,500 students and 4,200 employees, it is today the largest medical training facility in the German-speaking region. With its 29 university departments, 12 medical-theoretical centres and numerous highly specialised laboratories, it also ranks amongst the most significant cutting-edge research institutions in Europe in the biomedical sector. Over 48,000 square metres of space have been dedicated to clinical research at the facility.
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Christopher Gerner
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University of Vienna