Thomas R. Cox, May 2016
In collaboration with the department of oncology and department of clinical and experimental medicine at Linköping University in Sweden, we have just published a new paper looking at the importance of lysyl oxidase (LOX) in rectal cancer patients.
Lysyl oxidase (LOX) in cancer
The importance of lysyl oxidase (LOX) in different types of solid cancer is the subject of intense debate among scientists working in the field. In particular, there is much discussion around whether the specific localisation of LOX protein (inside vs. outside the cell) and the exact form of the protein (mature vs immature) have opposing roles.
These differences are critically important since they may lead to alternative recommendations when it comes to potential patient treatments in the future. Thus there is a need to deepen our understanding of when, and where, LOX is expressed in solid cancers and the importance of these differences.
LOX in normal and cancer tissue
In this study, we looked at the the patterns of expression of LOX in normal intestine close to tumours, within the tumours themselves, and finally in other nearby organs where the tumours had spread to (metastases). We found that in the cancer samples, LOX expression inside the cancer cells is higher than it is inside cells found in normal tissue. This suggests that LOX is important to the cancer cells somehow.
What was more interesting was that we see a larger increase in LOX protein in the cancer cell nucleus (the storage compartment for the cells genetic material), when the cancer cells have spread to other parts of the body. Therefore, our findings suggest that the specific localisation of LOX inside the cell may be an important marker of the spread of rectal cancer around the body.
We also noted that when patients were given radiotherapy, the standard treatment for rectal cancer patients, that this did not affect the level of expression of LOX in the cancer cells. Importantly, this means that we could use LOX expression as a biomarker for predicting patients in which their cancer may have spread to other parts of the body.
Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical signi cance of this expression. Nuclear LOX expression was signi cantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the rst to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.
Liu N, Cox TR, Cui W, Adell G, Holmlund B, Ping J, Jarlsfelt I, Erler JT, Sun XF. Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients. Oncotarget. 2016 May 26. doi: 10.18632/oncotarget.9623
The study was supported by grants from the Swedish Cancer Foundation, the Research Council of South East Sweden, and Liu Cancer.