Abstract 30P
Background
One of the risk factors to develop colorectal cancer (CRC), which is one of the deadliest types of cancer, is inflammation. Among the factors involved in the inflammatory response, prostaglandins (PGs) seem to play an important role. The tumor microenvironment (TME) influences the development of the tumor and within the TME, cancer associated fibroblasts (CAFs) represent the major compartment. Despite the importance of the TME, there is limited evidence on the secretome-dependent communication of CRC cells with CAFs and myeloid cells with respect to PG signaling. In this project we mainly focus on PGE2 and PGF2α, that we have previously found are secreted by CAFs.
Methods
By using in vitro 3D cocultures secreted molecules induced by increased or decreased PGE2 and PGF2α expression were identified. The levels of both PGs were measured by ELISA, whereas the expression of the production enzymes was analyzed by Western Blot. Phenotypic analysis and functional assays were carried out using siRNA or specific inhibitors to analyze the effect on angiogenesis and contractility of CAFs, their proliferation, motility, and apoptosis levels. Finally, preliminary in vivo experiments were performed and, additionally, paraffin tissue sections from patient-derived xenografts (PDX) models were stained to prove the stroma expression of the PGs specific synthases.
Results
We demonstrate that a combination of proinflammatory cytokines can increase the expression of COX-2 and mPGES-1 while IL-4 decreases it. Knocking down the specific synthases of PGE2 and PGF2α in the CAFs also leads to a decrease in their proliferation, contractiliy, motility and angiogenesis capacity, but did not induce apoptosis. In vivo, knocking down of the PGs specific synthases seems to lead to a worse survival capacity, and some of these enzymes seem to be only expressed in the stromal cells of PDX models.
Conclusions
More information about the link between cancer and its TME would help us to achieve a higher degree of accuracy in the development of potential future therapies. Here we have proved that the action of PGs, especially PGF2α and PGE2, is involved in tumor development in 2D and 3D suggesting a possible therapeutic target.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Marie Skłodowska-Curie Actions - PhD Research Fellowship. European Commission (Horizon 2020).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
57P - Metastasis organotropism: Unveiling associated proteins using network biology
Presenter: Margarida Carrolo
Session: Poster session 09
59P - Correlation of tumor microenvironment signature in advanced stage non-small cell lung cancer with EGFR mutation who received EGFR-TKIs
Presenter: Chaiyapong Ngamchokwathana
Session: Poster session 09
60P - Establishment and characterization of a novel lung adenocarcinoma cell line HX-JCJ harboring MET ex14 skipping mutation
Presenter: Xuejin Ou
Session: Poster session 09
61P - Next generation sequencing and its clinical utility in advanced cancer: Single institute experience from low-middle income country
Presenter: Amit Badola
Session: Poster session 09
62P - Prebiotics modulate gut microbiota-mediated T cell immunity to enhance sintilimab inhibition of lung cancer
Presenter: QIN YAN
Session: Poster session 09
63P - Addition of human chorionic gonadotropin to the current standard mobilization approach with granulocyte-colony stimulating factor increases overall survival in a murine model of peripheral blood stem cell transplantation: Are we far enough for therapy?
Presenter: Andrei Cismaru
Session: Poster session 09
64P - Developing novel therapeutics for bladder cancer leveraging drosophila models
Presenter: Takuya Moriguchi
Session: Poster session 09
65P - Ionizing radiation induces vascular smooth muscle cell senescence through activating NF-κB-CTCF-p16 pathway
Presenter: xuefeng zheng
Session: Poster session 09
66P - Exploring the radiobiology and dosimetry of targeted alpha therapy as a tool to optimize its clinical application: A preclinical study
Presenter: Maria Filomena Botelho
Session: Poster session 09
67P - The effect of non-viral gene-immune therapy via OX40L or 4-1BBL on murine subcutaneous CT26 colon cancer model
Presenter: Olga Rakitina
Session: Poster session 09