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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5071 - Acquired chemoresistance of colorectal cancer (CRC) cells is accompanied by pro-invasive VEGF-signaling that can be attenuated by aflibercept

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Annette LARSEN

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

A.K. LARSEN1, P. van Dreden2, B. Chibaudel3, A. de Gramont4, G. Gerotziafas5, S. Thouroude6

Author affiliations

  • 1 Cancer biology And Therapeutics, Centre De Recherche Saint-antoine, Hôpital Saint-Antoine, INSERM U938 & Sorbonne University, 75571 - Paris/FR
  • 2 Laboratoire Rd, Diagnostica Stago (SAS), 92230 - Gennevilliers/FR
  • 3 Medical Oncology, Institut hospitalier Franco-Britannique/ Franco-British Institute, 92300 - Levallois-Perret/FR
  • 4 Medical Oncology, Institut hospitalier Franco-Britannique, 92300 - Levallois-Perret/FR
  • 5 Cancer biology & Therapeutics, APHP, CancerEst, Tenon University Hospital, 75020 - Paris/FR
  • 6 Cancer biology And Therapeutics, Centre De Recherche Saint-antoine, INSERM U938 and Université Pierre et Marie Curie (UPMC), Sorbonne Universités Paris, France, 75006 - Paris/FR
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Resources

Abstract 5071

Background

Cancer mortality is principally associated with the presence of drug-resistant, invasive subpopulations of tumor cells. However, the functional and mechanistic interactions between the two phenotypes are incompletely understood. Colorectal cancer (CRC) cells produce the vast majority of VEGF in the cancer environment and display endogenous VEGFR1/VEGF signaling which is believed to promoted survival under stress.

Methods

Migration and invasion was determined by the transwell assay (Boyden Chamber). For the tube formation assay, CRC cells were seeded onto 3D matrigels and incubated at 37° for 24 hr monitored by videomicroscopy. Determination of VEGF ligands was carried out by ELISA.

Results

We here characterize a panel of 4 isogenic CRC cell lines comprised of the parental HCT-116 cells and three independently derived sublines resistant to 5-fluorouracil, oxaliplatin and SN-38. Resistant cells secreted 3-7 fold more VEGF, while the HCT-116/5-FU cells also secreted 2 times more PlGF, compared to the parental cells. VEGF signaling is known to promote CRC cell migration and invasion. In agreement, resistant cells showed 6-11 fold increased migration, whereas the invasive capacity had increased 6-15 fold. Aflibercept inhibits all three VEGFR1 ligands (VEGF-A, VEGF-B and PlGF) on CRC cells. Accordingly, addition of aflibercept resulted in a significant decrease in both migration and invasion. Two of the three resistant cell lines were able to do vascular/vasculogenic mimicry by forming capillary-like cellular networks which could be significantly attenuated by aflibercept.

Conclusions

Taken together, our results indicate that acquired resistance to genotoxic agents may be accompanied by an increased invasive potential mediated, in part, by VEGF signaling that can be attenuated by aflibercept.

Clinical trial identification

Legal entity responsible for the study

INSERM and Sorbonne University.

Funding

Financed in Part by Sandofi-Aventis Europe.

Editorial Acknowledgement

Disclosure

A.K. Larsen: Research grant: Sanofi-Aventis Europe. All other authors have declared no conflicts of interest.

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