Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 09

29P - The effect of cancer associated fibroblast-derived activin A on colorectal cancer progression

Date

21 Oct 2023

Session

Poster session 09

Topics

Basic Science

Tumour Site

Colon and Rectal Cancer

Presenters

Simone Stang

Citation

Annals of Oncology (2023) 34 (suppl_2): S187-S214. 10.1016/S0923-7534(23)01931-2

Authors

S. Stang1, L. Armborst1, S. Hilberath1, E. Koncina2, M. Macia-Guardado1, M. Hengstschläger1, E. Letellier2, H. Dolznig1

Author affiliations

  • 1 Institute Of Medical Genetics, MedUni Wien - Medical University of Vienna, 1090 - Vienna/AT
  • 2 Department Of Life Sciences And Medicine, University of Luxembourg, 4367 - Belvaux/LU

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 29P

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. In particular, the yearly mortality emphasizes the limited spectrum of treatment possibilities. The tumor microenvironment with its relevant influence on malignant tumor initiation, progression and chemoresistance represents a promising target for cancer therapeutics. Especially cancer-associated fibroblasts (CAFs) are of importance in carcinogenesis as they are involved in tumorigenesis, metastasis, inflammatory responses, and extracellular matrix changes. Based on preliminary data, we found upregulated expression of INHBA, a gene encoding for the βA subunit of the TGFβ superfamily members Activin A, Activin AB and Inhibin A, in the stromal compartment of human CRC. Therefore, we wanted to investigate the autocrine and paracrine functional consequences of CAF-secreted Activin A in CRC.

Methods

We knocked down INHBA in primary patient-derived CAFs and used in vitro 3D collagen gel assays, flow cytometry, immunofluorescence, secretome analysis and Western blotting to check the autocrine effects of Activin A on CAFs. Regarding the paracrine impact on tumor cells and immune cells, we employed 3D co- and triple-culture collagen gel assays to determine the impact of CAF-derived Activin A. Here, we focused on proliferation, apoptosis and invasion levels of tumor cells as well as on monocyte differentiation, myeloid cell plasticity and T-cell activation.

Results

Our data demonstrate that CAFs expressing INHBA show a pro-proliferative, pro-motile and pro-contractile phenotype. Furthermore, the secretome and plasticity of CAFs were notably modified by the INHBA knockdown. Additionally, CAF-derived Activin A seems to influence various aspects of tumor progression and the plasticity of immune cells.

Conclusions

Together, our results indicate key functions of CAF-derived Activin A in CRC progression suggesting a potential novel therapeutic target.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Austrian Academy of Sciences.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.