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. 2020 Jun;146(6):1427-1440.
doi: 10.1007/s00432-020-03186-x. Epub 2020 Apr 6.

Expression of Pro-Angiogenic Factors as Potential Biomarkers in Experimental Models of Colon Cancer

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Expression of Pro-Angiogenic Factors as Potential Biomarkers in Experimental Models of Colon Cancer

Simona Delle Monache et al. J Cancer Res Clin Oncol. .

Abstract

Purpose: RAS mutational status in colorectal cancer (CRC) represents a predictive biomarker of response to anti-EGFR therapy, but to date it cannot be considered an appropriate biomarker of response to anti-VEGF therapy. To elucidate the function of K-Ras in promoting angiogenesis, the effect of conditioned media from KRAS mutated and wild type colon cancer cell lines on HUVECs tubule formation ability and the correspondent production of pro-angiogenic factors have been evaluated by a specific ELISA assay.

Methods: Ras-activated signaling pathways were compared by western blot analysis and RTq-PCR. In addition, VEGF, IL-8, bFGF and HIF-1α expression was determined in K-RAS silenced cells. Furthermore, we conducted an observational study in a cohort of RAS mutated metastatic CRC patients, treated with first-line bevacizumab-based regimens, evaluating VEGF-A and IL-8 plasma levels at baseline, and during treatment.

Results: K-RAS promotes VEGF production by cancer cell lines. At the transcriptional level, this is reflected to a K-RAS dependent HIF-1α over-expression. Moreover, the HIF-1α, VEGF and FGF expression inhibition in KRAS knocked cells confirmed these results. Within the clinical part, no statistically significant correlation has been found between progression-free survival (PFS) and VEGF-A/IL-8 levels, but we cannot exclude that these biomarkers could be further investigated as predictive or prognostic biomarkers in this setting.

Conclusion: Our study confirmed the direct involvement of K-Ras in promoting angiogenesis into colon cancer cell lines.

Keywords: Angiogenic factors; Colon cancer; IL-8; VEGF.

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