Molecular Biology Report: IL13Rα2 and Breast Cancer Metastasis

This molecular biology report investigates the role of IL13Rα2 in basal-like breast cancer metastasis. The study employs gene expression profiling and in silico analysis to determine the impact of targeting IL13Rα2. The research reveals that overexpression of IL13Rα2 increases lung metastasis, while the IL-13-STAT6-TP63 pathway acts as an antimigratory signaling molecule. The methodology includes lentivirus-mediated gene knockdown, bioluminescence imaging, microarrays, and cell migration tests. The findings suggest that IL13Rα2 could be a therapeutic target, potentially amplified to increase IL-13-STAT6-TP63 expression and reduce metastasis. The report also acknowledges the involvement of the orphan chemokine CXCL17. The study aims to provide insights into potential treatments for breast cancer by modulating the IL13Rα2 pathway and its downstream effects on metastasis.

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Molecular Biology
Student’s Name
Date of Submission

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Introduction and background
This research was designed bearing in mind the increased cases and mortalities associated
with breast cancer. More specifically is the basal like breast cancer in which the cancer cells
move to distant tissues and make them different to treat. For instance, the breast cancer cells may
move to the tissues where they metastasize and further form lesion on these tissues (Le et al.,
2014). Research however indicates that the basal breast cancer cells depends on making
alterations on both genetic as well as epigenetic mechanisms in order to complete the process of
metastasis. This study was thus set up to find out whether targeting some genes can be important
in the treatment of basal like breast cancer (Mavaddat et al., 2015). The interleukins are
important in cell processes and thus are in significant numbers in cancer cells. The interleukins,
for instance IL 3 is involved in cell growth, maturation and differentiation. More specifically,
IL13Rα2 and IL13Rα1 compete for the binding to their receptors and can be used
interchangeably. Previous gene profiling of IL13Rα2 indicated that this gene is abundant in lung
metastasis but its role in cancer has not been clear (Papageorgis et al., 2015). As such, unbiased
gene profiling using basal breast cancer was used to determine the roles of IL13Rα2 in
metastasis.
Methodology
The major method used in this experiment was the gene expression profiling as well as
the in silico leveraging of pre-existing breast tumor transcriptomes. In this case, the interleukin
13 receptor alpha 2 was knocked through the mediation of lentivirus. This was accompanied by
imaging process which made use of bioluminescence to determine the role of this interleukin in
breast cancer and metastasis in the lungs (Papageorgis et al., 2015). Further, confirmatory tests
were carried out using microarrays and cell migration tests to better understand the molecular

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pathways which play part in basal breast cancer and lung metastasis. A weakness of this gene
profiling method is that it is not possible to determine the roles of other genes like serpin B3,
serpin B4 and CD36 which are also regulated by interleukin 13. Since this is a genetics approach,
the biochemical methods which would have been used would be the Elisa tests. In this case,
antibodies specific for the IL13Rα2 interleukin would be directed to specific sites in the breast
and lung tissues. These would then be coupled with a secondary antibody which is specific for
the breast cancers and the reaction measured via the spectrophotometer for either light
absorbance or transmittance at a given wavelength.
Results
The authors were able to prove their hypothesis that when IL13Rα2 targets IL-13-
STAT6-TP63, it alters the breast cancer metastasis. The authors in this research concluded that
when there is an overexpression of the IL13Rα2 leads to increased metastasis in the lungs in
some sunsets of basal like breast cancer. Moreover, for the first time, it has been discovered that
there exists IL-13-STAT6-TP63 which is an antimigratory signaling molecule which can reduce
the rate if metastasis in the breast cancer cells. The control experiment which was used in this
research was the histology and immunochemistry in order to make confirmation of the results of
microarray analysis on the role of IL13Rα2 in metastasis. It is this assumed that the IL13Rα2 can
be used for therapeutic purposes to treat breast cancer (Papageorgis et al., 2015). This could be
done by amplifying the gene coding for IL13Rα2 such that it leads to the increased expression of
IL-13-STAT6-TP63 which in turn lowers the rate of metastasis in the lungs and other tissues in
patients suffering from breast cancer. The observed results could also be as a result of the orphan
chemokine CXCL17 which is regulated by IL-3 genes and facilitates progression to cancer
(Matsui et al., 2012).

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References
Le, M. T., Hamar, P., Guo, C., Basar, E., Perdigão-Henriques, R., Balaj, L., & Lieberman, J. (2014).
miR-200–containing extracellular vesicles promote breast cancer cell metastasis. The Journal of
clinical investigation, 124(12), 5109.
Matsui, A., Yokoo, H., Negishi, Y., Endo-Takahashi, Y., Chun, N. A., Kadouchi, I., ... & Kobayashi, E.
(2012). CXCL17 Expression by Tumor Cells Recruits CD11b+ Gr1highF4/80− Cells and
Promotes Tumor Progression. PloS one, 7(8), e44080.
Mavaddat, N., Pharoah, P. D., Michailidou, K., Tyrer, J., Brook, M. N., Bolla, M. K., ... & Luben, R.
(2015). Prediction of breast cancer risk based on profiling with common genetic variants. JNCI:
Journal of the National Cancer Institute, 107(5).
Papageorgis, P., Ozturk, S., Lambert, A. W., Neophytou, C. M., Tzatsos, A., Wong, C. K., ... &
Constantinou, A. I. (2015). Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress
breast cancer lung metastasis. Breast Cancer Research, 17(1), 98.