How Cancer Recuits Cells

An Overly Friendly Environment Study at the Faculty of Medicine: how a malignant tumor recruits the cells that support it

A study at the Technion’s Rappaport Faculty of Medicine sheds light on one of the malignant tumor’s survival mechanisms: cancer cells’ ability to induce their own supportive growth environment. The study, published in the journal Stem Cells, is the work of Liron Berger (as part of her doctoral dissertation) and Yeela Shamai, under the guidance of Dr. Maty Tzukerman in collaboration with Prof. Karl Skorecki at the Molecular Medicine Laboratory.

Dr. Maty Tzukerman

During evolution, malignant tumors developed sophisticated survival mechanisms. One of them is the recruitment of healthy cells for the development of supportive tissue (stroma), which is a tumor micro-environment that promotes its growth and development.

The malignant tumor contains both cancer cells and stromal cells, and the aim of this study was to characterize the interactions between these two types of cells. To this end, the researchers isolated stromal cells from malignant tumors of anonymous patients, and grew them in the laboratory. They found that the tumor-derived stromal cells were identified as mesenchymal stem cells (MSCs) – cells that have the potential to differentiate into adipocytes, osteoblasts and chondrocytes.

The researchers examined the relationship between the tumor- derived cancer and stromal cells, and found that tumors behave differently in this regard: while the lung-cancer cells growth is independent of their stromal cells, the gastric cancer cells growth was critically dependent on the presence of their counterpart stromal cells or their conditioned medium. This dependency was also observed in in vivo experiments.

According to the researchers, The finding that none of the various other tumor-derived MSC were able to restore the specific effect of these stromal cells on the cancer cell growth, indicates exquisite specificity whereby tumor-derived MSCs are specifically recruited and ‘educated’/reprogrammed by the cancer cells to support tumor growth. Dr. Tzukerman said, “It turns out that gastric cancer cells do not express the human growth factor (HGF) gene, which is required for tumor progression, and therefore they are dependent on their counterpart stromal cells which express this gene. Our hypothesis was that cancer cells of various types summon the stromal cells that are vital to them.”

Stromal cells (stained red or green) and cancer cells (nuclei stained blue) produced from a malignant stomach tumor

To test their hypothesis, the researchers developed a method that simulates the recruitment of cells from a healthy tissue into the tumor. The findings: gastric cancer cells proactively attract mesenchymal stem cells that express the human growth factor (HGF) gene that is crucial for their growth. Lung cancer cells, on the other hand, attract mesenchymal stem cells that do not express the HGF protein. The mesenchymal stem cells ‘recruited’ into the gastric tumor eventually undergo reprogramming to enhance the expression of HGF, thereby creating an optimal environment for the tumor cancer cells.

According to Dr. Tzukerman, “The study constitutes an additional level of cancer heterogeneity which has to be taken into consideration in anti-cancer therapeutic approaches tailored for targeting and overcoming each distinct tumor.