Abstract 57P
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.
Resources from the same session
4P - Spatially resolved transcriptome elucidates bidirectional tertiary lymphoid structure interacts with tumor microenvironment of non-small cell lung cancer
Presenter: Xin Zhao
Session: Poster session 09
5P - Tertiary lymphoid structures (TLS) presence and stromal blood vessels heterogeneity differentially influence recurrence, lymphovascular, and perineural invasion in breast cancer molecular subtypes
Presenter: Andrei Cosma
Session: Poster session 09
6P - Combined single-cell and spatially resolved mapping of the human lymph node ecosystem reveals fundamental principles of lymphoma tissue organization
Presenter: Daniel Hübschmann
Session: Poster session 09
7P - Engineered salmonella blocks cancer metastasis by activating NK cells in an IFN-γ-dependent manner
Presenter: JIANDONG HUANG
Session: Poster session 09
8P - Modulating tumor microenvironment using a VEGF active immunotherapeutic approach in gastrointestinal tumors: Beyond angiogenesis modulation
Presenter: Mónica Bequet-Romero
Session: Poster session 09
9P - Identification of a μCT-based radiomic signature of CD8+ tumour infiltrating lymphocytes in an orthotopic murine model
Presenter: Giulia Mazzaschi
Session: Poster session 09
10P - Cancer cells induce intracellular gap formation in sinusoidal endothelial cells to produce liver metastasis through pro-inflammatory paracrine mechanisms
Presenter: Hoang Truong
Session: Poster session 09
11P - Targeting stromal cells to reverse immune suppression in triple-negative breast cancer
Presenter: Julia Chen
Session: Poster session 09
12P - Immuno-suppressive role of tumour-derived GDF-15 on myeloid cells
Presenter: Christine Schuberth-Wagner
Session: Poster session 09
13P - Disrupting the immunosuppressive tumor microenvironment using genetically engineered macrophages for triple-negative breast cancer therapy
Presenter: Sabrina Traxel
Session: Poster session 09