A new function of the HOPX gene, which places it among the not very numerous group of genes responsible for the change of the cell of the primary tumour into a metastatic cell, was described by a scientific team at the Institute of Molecular Genetics of the ASCR led by Dr. Jiří Hejnar. Their discovery was published in August this year in the international journal Molecular Cancer Research (see abstract). It is a generally known fact that in tumour illnesses the main cause of death in patients are precisely metastases, the secondary centres of the tumour scattered in distant organs and tissues, which resist surgery, radiation and are not very sensitive to chemotherapy.
What causes the originally nonmetastatic cancer cell to be able to travel from the primary
tumour, enter the bloodstream, leave it at another place and establish a secondary centre,
metastasis? How is this complicated process of change governed and who gives the command for such a
change? One of the ways scientists attempt to answer such questions is a comparison of the
expression (‘switching on’) of genes in nonmetastatic and metastatic cells, because ‘behind
everything, look for genes’ applies even here.
A fundamental complication of such a scientific approach is, however, the great genetic
diversity of the cells already in the primary tumour. It is therefore necessary to use models where
the primary tumour is evoked on a one-time bases, for instance by a retrovirus, and when the number
of changes present in the secondary metastases is limited. The genes in which we find differences
are then likely engaged in the process of metastasis and their real effects can be tested in cell
lines or experimental animals. It is subsequently possible to seek in a targeted way whether the
changes in those genes are present are in the metastases of human tumours and use that knowledge
for treatment. The main genes that have been described in connection with the emergence of
metastases include intuitively those which affect the mobility of cells, their ability to grow
through healthy tissues and survive in the circulatory system.
Thanks to the efforts of researchers from the Institute of Molecular Genetics of the ASCR
1,the as-yet short list of such genes was expanded by the
HOPX gene, which had as yet been only vaguely connected with the regulation of other genes,
with the development of the heart and with the emergence (but not with metastasis) of some types of
tumours. The crucial model for the identification of the
HOPX gene were chicken tumours evoked by a retrovirus, which were studied in the long term
and in which there are metastatic and nonmetastatic varieties. As the scientific team under the
guidance of Dr. Hejnar describes in its latest publication,
HOPX cats here as an activator of the creation of metastases and on the other hand
suppression of the expression of the
HOPX gene leads to a reduction of the metastatic activities of these retrovirus-evoked
chicken tumours.
Current scientific results often emerge in parallel in many places. A methodologically very
similar study was published almost at the same time by researchers from the Yale University School
of Medicine
2 (see
abstract), this time with the use of laboratory mice. Both of these works
investigate various types of tumours (whether they be tumours created from connective or epithelial
cells), and so they complement one another. Which partial processes of metastasis are influenced by
the
HOPX gene can be inferred from the differences.
In the end, it is necessary to point out that not only research based on strains of laboratory
mice has its place in experimental oncology. This scientific work shows that equivalent results can
be provided also by sometimes ignored models, particularly well defined lines of hens, which offer
a unique possibility for the study of tumours, viruses and immune responses. A comparison of the
results acquired from animals of various distances from humans in terms of development then
confirms which riles are generally valid and which could be species specific.
You can find more information in these publications:
1Kovářová D., Plachý J., Kosla J., Trejbalová K., Čermák V., Hejnar J. Downregulation of
the HOPX gene decreases metastatic activity in a chicken sarcoma cell line model and identifies
genes associated with metastasis. Molecular Cancer Research, Aug 12. [Epub ahead of print]
2Cheung W. K., Zhao M., Liu Z., Stevens L. E., Cao P. D., Fang J. E., Westbrook T. F.,
Nguyen D. X. Control of alveolar differentiation by the lineage transcription factors
GATA6 and
HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell 23: 725-738, 2013
Contact: RNDr. Jiří Hejnar, CSc., Institute of Molecular Genetics, ASCR, tel.: 241
063 443, mobile: 774 798 142
Prepared by: The Institute of Molecular Genetics of the ASCR and the Department of Media
Communication of the Head Office of the ASCR
19 Sep 2013
