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.
Resources from the same session
2300 - AXL has a prognostic role in metastatic colorectal cancer (mCRC) and is a predictive biomarker of lack of efficacy of chemotherapy (CT) + cetuximab in RAS wild type (WT) patients (pts)
Presenter: Claudia Cardone
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
Resources:
Abstract
2834 - Multimodal detection of homologous recombination repair gene mutations (HRRm) in a Phase II trial of olaparib plus abiraterone in metastatic castrate resistant prostate cancer (mCRPC)
Presenter: Thomas Carr
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
Resources:
Abstract
3596 - Identification of a highly suppressive Treg subset associated to immunotherapy response
Presenter: Emilio Giunta
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
Resources:
Abstract
3705 - A Novel Framework for Evaluating Biomarker Response Relationships in Immuno-oncology (IO)
Presenter: Jeffrey Evelhoch
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
Resources:
Abstract
5332 - Comparison of OncoBEAM and NGS methods to detect plasma EGFR T790M mutations at progression of NSCLC
Presenter: Jessica Garcia
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
Resources:
Abstract
5700 - Differential expression of PD-L1 and immune biomarkers by age: Decreased expression in pediatric/AYA patients with advanced cancer
Presenter: Omid Hamid
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
Resources:
Abstract
966 - Potential resistance mechanisms revealed primary resistance to crizotinib in ROS1+ non-small-cell lung cancer using next generation sequencing: A multicenter study
Presenter: Quxia Zhang
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
Resources:
Abstract
2171 - Prevalence of CLDN18.2, HER2, and PD-L1 in Gastric Cancer Samples
Presenter: Diarmuid Moran
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
Resources:
Abstract
2318 - Epigenetic markers in circulating cell-free DNA for detection of early stage colorectal cancer
Presenter: Yanqun Liu
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
Resources:
Abstract
3625 - Detection and clearance of RET variants in plasma cell free DNA (cfDNA) from patients (pts) treated with LOXO-292
Presenter: Benjamin Besse
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
Resources:
Abstract