57P - Metastasis organotropism: Unveiling associated proteins using network biology

Background

The formation of distant metastases is the deadliest phase of cancer progression. Nevertheless, it is a very inefficient process. Chances of a tumor cell surviving the metastatic process depend on its ability to communicate with the surrounding environment. We hypothesize that metastasis organotropism can be partially explained by the intercellular communication established between cancer cells and other cells in the organ microenvironment.

Methods

Network biology tools are well suited for studying complex diseases such as cancer. Using this computational approach we looked at the complex interplay between proteins and pathways affected in metastasis and identified new metastasis-associated proteins. We built networks of tissue-specific intercellular protein-protein interactions between pairs of primary tumor location and metastasis tissues. Using these networks we identified interactions significantly more frequent in organotropism tissue pairs (primary tumor and metastasis organ) that potentially influence the success of metastasis in specific organs.

Results

Overall, we identified 607 proteins involved in 1095 metastasis-associated interactions. Of these, 881 interactions were positively associated with metastasis, meaning that these interactions occur more frequently in organotropism tissue-pairs than in other tissue pairs. Of the 607 proteins found, 222 are already targeted by known drugs and 53 are targeted by drugs that are not used in cancer treatment.

Conclusions

Cell-cell communication is of paramount importance for the development of metastasis. Experimental studies of the non-oncological drugs targeting the 53 identified proteins are needed to select the most promising candidates to test in drug repurposing clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.