Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


'Genomic catastrophe' may cause normal cells to become cancerous


Aberrant cell fusion may initiate cancerous processes and tumor formation, according to a new study published in the American Journal of Pathology

Although there is no one established universal cause of cancer, genetic changes are central to its development. The accumulation of spontaneous genetic changes, or mutations, that occur when cells divide can be hastened by exposure to carcinogens such as cigarette smoke (lung cancer) and infectious agents such as the papillomavirus (cervical cancer).

Typical image of fused cell sorted by FACS and visualized by fluorescence microscopy. The fused cell emits both CFSE (green) and SNARF-1 (red) fluorescence; the image represents at least 50 cells examined per experiment. Scale Bar: 5 µm

Courtesy of the American Journal of Pathology

However, some researchers believe that spontaneous mutations are too infrequent, and the link between carcinogens and genetic changes too uncertain, to fully explain the development of some of the most common cancers. The results of this study may provide an explanation: that fusion of one normal cell with another -- as observed in inflammation, infection, and injury from carcinogens -- triggers a 'genomic catastrophe' that converts normal cells to cancer cells and enables tumors to form.

Cell fusion is a process in which one or more cells combine to form a new cell with more than one nucleus. Cell fusion has been postulated as a possible cause for some cancers because it could explain the occurrence of multiple genetic changes thought to underlie cancer.

However, direct evidence that fusion of normal cells by itself could trigger cancer has not been reported. Now, a new study published in The American Journal of Pathology provides the missing link between a single untoward event, cell fusion, and the multiple catastrophic genetic changes that ultimately transform normal cells into cancerous cells. Furthermore, when injected into live animals, these aberrant cells form tumors.

Researchers from the University of Michigan and the Mayo Clinic studied rat IEC-6 intestinal epithelial cells, chosen because they maintain a stable diploid genomic structure (two sets of chromosomes), lack the cellular characteristics of cancer cells, and replicate normally. They also do not form tumors when monitored over many generations.

IEC-6 cells were labeled with either red or green fluorescent dyes. The cells were then exposed to 50 percent polyethylene glycol to encourage cell fusion. The fused cells were identified by the presence of both red and green dyes within one cell, whereas nonfused cells displayed only one color. Fused cells were also larger than non-fused cells.

Investigators made several important observations. First, they showed that fused cells could replicate, with 19 percent of fused IEC-6 cells establishing clones and that with replication the chromosomes from the two cells intermixed. They also observed that 41 percent of the clones had abnormal numbers of chromosomes (aneuploidy), 56percent were near-diploid (40 to 44 chromosomes), and 4 percent were tetraploid (84 chromosomes), whereas the large majority (86 percent) of non-fused cells were diploid.

'These results indicate that cell fusion generates chromosomal instability,' explained lead investigator Jeffrey L. Platt, M.D., professor of surgery and microbiology and immunology, Departments of Microbiology and Immunology and Surgery, University of Michigan (Ann Arbor). Chromosomal instability refers to changes in the number and appearance of chromosomes in a species.

Because aneuploidy and chromosomal abnormalities are commonly observed in cancer, the researchers looked for evidence of DNA damage in the fused clones. The double-strand DNA break marker phosphorylated H2AX revealed breaks in significantly more fusion-derived clones than in nonfused clones (35 percent to 42 percent versus 4 percent to 9 percent, P < 0.0001). This finding suggests that after cells fuse, chromosomal instability might lead to DNA damage and hence to genetic changes that underlie cancer. Consistent with that possibility, fused cells often exhibited the same abnormal growth characteristics as cancer cells.

'The frequency of cell fusion events in vivo is not known, although cell fusion is thought to occur under some circumstances such as cell injury, inflammation, and viral infection. Although fusion of normal cells in vitro and in vivo may be a rare event, this study shows that cell fusion between normal cells can have pathological consequences,' commented noted authority and cancer specialist William B. Coleman, Ph.D., of the Department of Pathology and Laboratory Medicine, Program in Translational Medicine at the University of North Carolina Comprehensive Cancer Center (Chapel Hill). 'The results provide evidence for another molecular mechanism driving neoplastic transformation - genomic catastrophe.'

Perhaps the most exciting observation occurred when fused IEC-6 cells were transplanted into immunodeficient mice. Over the course of 12 weeks, these cells generated tumors in 61 percent (11/18) of the hosts whereas no tumors formed from the parental IEC-6 cells or IEC-6 cells that did not fuse. Furthermore, only those fusion-derived IEC-6 cell clones that had undergone the changes in cellular growth indicative of neoplastic transformation produced tumors in mice.

'We believe one cell fusion event can both initiate malignancy and fuel evolution of the tumor that ensues,' noted lead author Xiaofeng Zhou, Department of Microbiology and Immunology and Surgery and the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, at the University of Michigan (Ann Arbor).

According to Coleman, most cases of spontaneous cancers in humans are thought to derive from cells that sustained random DNA damage or random errors during DNA replication. 'Zhou et al provide evidence for a different mechanism of spontaneous neoplastic transformation. The observations suggest strongly that genomic catastrophe can produce the required and necessary molecular alterations for neoplastic transformation and tumorigenesis in normal founder cells in the absence of selective pressures or ongoing genomic evolution.' Coleman added that further research is needed to determine whether cell fusion events between normal human cell types result in genomic catastrophe and neoplastic transformation.

Eileen Leahy | EurekAlert!

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>