Spurred by the knowledge that 90 percent of cancer deaths are caused by metastases, a research team at Johns Hopkins has discovered a mechanism that tells cancer cells to migrate and take up residence in other parts of the body. The same team has also shown that a two-drug combination can slow the number of cancer cells on the move.
Using 3D cell cultures to identify what drives cancer cells to move, the team zeroed in on the relationship between rapid cell reproduction and tightly packed living quarters.
Research team member Hasini Jayatilaka (a postdoctoral fellow at Johns Hopkins’ Physical Sciences-Oncology Center) says: “It’s like waiting for a table in a severely overcrowded restaurant and then getting a message that says you need to take your appetite elsewhere.”
The team discovered “the message” is transmitted by Interleukin 6 (IL-6) and Interleukin 8 (IL-8); cell proteins produced by the two types of cancer cells when crowded conditions exist. It results in a behaviour change – in this case for cancer cells to move using the lymph system or bloodstream as travel routes.
The researchers point out that had it not been for the 3D cultures employed, the cell-density-dependent migration of cancer cells might never have been observed and they state that future cancer researchers should use 3D cultures.
One of the study’s senior authors, Denis Wirtz, the University’s vice provost for research and director of its Physical Sciences-Oncology Center, says drug development thus far has focussed on destroying the primary tumour as the best way to prevent metastasis.
With the goal of inhibiting the communication pathway initiated by IL-6 and L-8 – the John’s Hopkins team used Tocilizumab (which is currently used to treat rheumatoid arthritis) and investigational cancer agent, Reparixin, in combination.
The team’s findings suggest the treatment could greatly decrease the metastatic capacity of tumours and potentially improve cancer patient outcomes.
The study is published online in the journal Nature Communications.
Written by: MaryAnne Pankhurst
Hasini Jayatilaka, Pranay Tyle, Jonathan J. Chen, Minsuk Kwak, Julia Ju, Hyun Ji Kim, Jerry H. S. Lee, Pei-Hsun Wu, Daniele M. Gilkes, Rong Fan & Denis Wirtz