Communication between cells: How tumour cells manipulate their environment

Cell biologists from Tel Aviv and molecular biologists from Heidelberg combine their know-how to explore mechanisms that make black skin cancer so dangerous – and to find better therapeutic approaches.

Autor: Stefanie Reinberger, Journalistenbüro Schnittstelle

Human cells are not isolated building blocks which exist independently from each other in tissue. Instead, they exist in a constant exchange: They obtain information on the neighbouring cells’ condition and total tissue structure, and send signals to each other to, for example, coordinate development or synchronize metabolic processes, thereby ultimately ensuring that the organism functions optimally.
Tumours also participate in this information exchange between somatic cells. “Initially, this is a very natural process”, emphasises Joerg Hoheisel, chair of the Department of Functional Genome Analysis at the German Cancer Research Centre in Heidelberg, DKFZ. Nevertheless, tumours are a communication exception: Instead of using their signals to aid a healthy functioning body, they appear to manipulate their environment for their own advantage, thereby securing optimal survival and growth conditions for themselves.

Fatal signals from the epidermis

Carmit Levy, group leader in the Department for Human Genetics and Biochemistry at the Tel Aviv University, is a specialist in the formation of these communication processes and how they contribute to the spreading of skin cancer, of malignant melanoma. The malignant melanoma is regarded as the most dangerous skin tumour and most fatal skin disease overall – with a globally increasing number of new diseases. Melanomas develop from abnormal pigment cells, the so-called melanocytes. At a very early stage of the disease, they already tend to spread in the body via blood and lymphatic circulation to form metastases in other organs. In addition, they are often therapy resistant.

Particularly critical for the disease’s progression, is the abnormal pigment cells’ migration from the epidermis to the dermis underneath which, in contrast to the epidermis, contains many blood vessels – a prerequisite for the spreading of the tumour. “Surprisingly, melanoma cells first direct themselves to grow upwards before they change direction, enter the dermis and become invasive”, Levy describes this phase’s peculiarity. This is actually illogical: Why should tumour cells waste energy to first grow upwards before entering the skin layers underneath? “This made me think that the tumour’s microenvironment must have a trigger that leads to the invasiveness of melanoma cells”, explains the Israeli scientist.

She and her team started searching for such a trigger, and were successful. A comparison of healthy and malignant skin samples showed the following: Keratinocytes, the keratin-producing epidermal cells, send out a ligand, which is a molecule that attaches to the melanoma cells and stimulates a signal path, eventually transforming these into invasive tumour cells.

Miniature messages support cancer

In addition, the scientist from Tel Aviv observes that the tumour also sends signals to its environment. Here, small RNA pieces, the so-called micro RNAs (miRNAs), play an important role. They can regulate genes in various ways, thereby influencing the cell’s behaviour.

However, in-depth specialised knowledge is necessary to decipher the molecular biological message of such miRNAs. Here, Joerg Hoheisel came on board. “I needed a cooperation partner who had miRNA analysis know-how, and Joerg Hoheisel was the best I could find”, said the cell biologist. Both teams in Tel Aviv and Heidelberg complemented each other perfectly: Here the specialists on malignant melanoma and cell-level processes, and there the miRNA and genome analysis experts.

“Until that point, I had never researched melanomas”, admits Hoheisel, whose work in Heidelberg actually focusses on pancreatic cancer. “But we can basically apply our methods and analytical procedures to any type of cancer, and I find the question which Carmit Levy pursues absolutely fascinating.” The scientist of the German Cancer Research Centre did not have to think twice before agreeing to the cooperation.

Cancer research hand in hand

The cell biologist from Tel Aviv and the molecular biologist from Heidelberg have been cooperating for three years now. “At first we exchanged intensive, long distance e-mail correspondence, but the more tangible the project became, the more important the face-to-face exchange became”, Hoheisel describes the collaboration in hindsight. Co-workers from both teams repeatedly visited each others’ laboratories for extended periods to conduct joint experiments.

The scientists from Heidelberg and Tel Aviv work hand in hand to decipher the mystery of the miRNA messages. The German-Israeli team is convinced that, in this manner, they will discover molecular biological mechanisms which contribute to the development of the tumour and give it an edge – for example, the malignant melanoma’s strong resistance against many otherwise successful cancer therapies. Similar to the metastasis formation results, this can contribute to a better therapy approach for successful treatment of the dreaded black skin cancer.