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
46P - Effect of coadministration of antioxidant chlorophyllin with docetaxel on invasion and metastasis in triple-negative breast cancer in vivo/in vitro
Presenter: Ayse Burus
Session: Poster session 09
47P - An ozone delivery system by cisplatin prodrug self-assembling micelles combining microwave to sensitizing immune checkpoint inhibitor in triple-negative breast cancer
Presenter: Dan Zheng
Session: Poster session 09
48P - Non-steroid anti-inflammatory treatment enhances the efficacy of modulated electro hyperthermia on triple-negative breast cancer and melanoma cancer models in vivo
Presenter: Nino Giunashvili
Session: Poster session 09
49P - Circulating miRNA signatures to predict recurrence in patients with pathological complete response of triple-negative breast cancer
Presenter: Ana Julia de Freitas
Session: Poster session 09
50P - Application and mechanism of tarloxotinib in HER2-positive breast cancer
Presenter: Xinyi Shao
Session: Poster session 09
51P - Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic breast tumour therapy by glutamine deprivation and cascading thrombosis
Presenter: Liqiang Zhou
Session: Poster session 09
53P - Treatment of cancer cells based on circulating tumor cell’s expression profile using off-label drugs
Presenter: Panagiotis Apostolou
Session: Poster session 09
54P - Enhanced oxidative phosphorylation of metastasis-initiating cells facilitates esophageal tumor cell seeding in lymph nodes
Presenter: Shanshan Li
Session: Poster session 09
55P - Transcriptional profiles of engineered T cells stimulated with different receptor structures and co-stimulatory domains
Presenter: Ungue Shin
Session: Poster session 09
56P - SLC34A2-ROS1 L2026M+G2032R confers resistance to ROS1 tyrosine kinase inhibitors in Ba/F3 cells through a reduced ATP binding pocket volume
Presenter: Christa Dijkhuizen
Session: Poster session 09