Living cells display an extraordinary capacity to sense the chemical and physical properties of the extracellular environment, and respond to environmental cues by altering their fate and behavior. Behind these interactions - particularly the adhesion of living cells to one and other, and to their surrounding environment - are a number of complex molecular mechanisms that likely contribute to the spread of cancer.
Prof. Benjamin Geiger from the Department of Molecular Cell Biology is investigating the role of cell-matrix and cell-cell adhesions in regulating collective cell migration.
This topic appears to be highly relevant to cancer metastasis, a process through which individual cells or small cell clusters are dislodged from the primary tumor, invade nearby blood and lymphatic vessels, and are carried to distant tissues - most commonly in the lungs, liver, or brain - where they form secondary tumors. It has been shown that collective cancer cell invasion increases the cancer’s ability to survive the metastatic process.
With the support of the Krenter Institute, Prof. Geiger has been able to study a novel form of collective migration, manifested in the highly metastatic 4T1 breast carcinoma cell line. These cells are considered to be an excellent model for metastatic cancer. Thus far, he has found that these cells migrate collectively even while maintaining long-distance tethers interconnecting them.
Prof. Geiger and his team are exploring the mechanisms of tether formation, their mechanical properties like strength and elasticity, the mechanism underlying their ability to harness migrating cells, and the cues the tethers transmit to neighboring cells to induce cell convergence. The characterization of this migratory mechanism may facilitate the development of reagents that will specifically interfere with this massive migration, and potentially reduce or block the dissemination of tumor metastases.
Image (left): van Roosmalen, W et al/Journal of Clinical Investigation, 125 (4):1648-1664.