Cancer Cells Trade Information and Proteins Through Nanotubes

Dr. Anne Burtey, PhD Department of Biomedicine, Biomaterials, Department of Clinical Dentistry and K. G. Jebsen Brain Tumour Research Center University of Bergen, Bergen, Norway; Department of Pathology and Department of Clinical Medicine Haukeland University Hospital, Bergen, Norway and NorLux Neuro-Oncology Laboratory, Department of Oncology Luxembourg Institute of Health Luxembourg, Luxembourg

Dr. Anne Burtey Interview with:
Dr. Anne Burtey, PhD
Department of Biosciences
University of Oslo
Oslo, Norway

Medical Research: What is the background for this study?

Dr. Burtey: At the site of tumors, cancer cells communicate with normal cells present in the microenvironment. This communication deeply modifies these cells that become “devoted” to tumors, helping the latter in growing, in becoming more invasive. Drugs blocking this communication – or taking advantage of it to spread better within tumors and towards “tumor-helper” cells – may represent a new generation of drugs with increased anti-cancer properties. To develop such drugs, we first need to understand the communication processes at stake between cancer and normal cells.

Previous reports suggested that cells communicate by trading entire subsets of components by contact- or secretion-dependent mechanisms. Whereas the latter is rather well studied, the former remains largely unclear. In 2004, our group identified tunneling nanotubes (TNTs) as a cellular feature for contact-dependent communication (Rustom et al., Science 2004). They are thin membranous bridges established between cells that facilitate the cell-to-cell transport of ions, proteins, RNAs, mitochondria and even viruses. That TNTs were observed in a variety of cells including cancer cells suggests that they may represent a general route of communication and play a role in cancer.

Medical Research: What are the main findings?

Dr. Burtey: Here, we found that cancer cells exchange proteins and organelles by TNTs – and contact-dependent communication – for which we characterized a marker and a key component of the molecular machinery involved. We showed that not only cancer cells use this communication process to communicate with each other, but also to communicate with normal cells.

Briefly, we developed new experimental approaches and identified the transferrin receptor (Tf-R) as a marker of TNT- and contact-dependent communication in cancer. We showed that the transfer of Tf-R between cancer cells is specific, contact-dependent but secretion-independent.  It requires the internalization of Tf-R in endosomes and the function of the small GTPase Rab8 that co-transfers with the receptor to neighboring cells.

Normal cells seem to be poor “traders” of Tf-R, but, in vivo, they are recipients of Tf-R transfer originating from tumor cells.

Surprisingly, we found that the transfer of Tf-R from tumor-to-normal cells may represent a “give me!” signal to which normal cells obey, and send back into tumor cells some of their own components. This may in turn represent a previously unrecognized “tumor-helping” function of normal cells.

Medical Research: What should clinicians and patients take away from your report?

Dr. Burtey: The message is that tumors are “super-traders” that exchange subsets of cellular components and send them into neighboring cells in order to get from those, in return, some of their constituents. Importantly, this trading can be now monitored and quantified in vitro and in vivo, and “tumor-helper” cells can now be specifically isolated from tumor masses for further analysis.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Burtey: Future research should consider using our in vitro approach to screen for drugs targeting tumor-helper cells or blocking tumor-organ communication. To study tumor-helper cells, one should consider using our in vivo model to specifically isolate them.    Finally, our findings may lead to the development of “super-spreading” anti-cancer agents that use nanotubes and cell-cell contacts to disseminate better within tumors and even reach corrupted tumor-helper cells that are present in the microenvironment. 


FASEB J. 2015 Nov;29(11):4695-712. doi: 10.1096/fj.14-268615. Epub 2015 Jul 28.

Intercellular transfer of transferrin receptor by a contact-, Rab8-dependent mechanism involving tunneling nanotubes.

Burtey A1, Wagner M2, Hodneland E2, Skaftnesmo KO2, Schoelermann J2, Mondragon IR2, Espedal H2, Golebiewska A2, Niclou SP2, Bjerkvig R2, Kögel T2,Gerdes HH2.

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Dr. Anne Burtey, PhD (2016). Cancer Cells Trade Information and Proteins Through Nanotubules