Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept
Figure 3
VEGFR-1 and VEGFR-2 differentially orchestrate the tumour-stroma interplay to promote cancer growth and metastasis. (a) Representative images of VEGFR-1 and VEGFR-2 immunostaining in a primary colon carcinoma and corresponding liver metastasis obtained from our still unpublished observations. Yellow and black arrows indicate the immunostaining in the stromal compartment and malignant colonic cells, respectively; with magnification 10x. (b) VEGFR-1 and VEGFR-2 immunostaining differentially correlate with CD68 infiltration, a marker of M2 tumor associate macrophages (TAMs). (c) Patients’ disease specific survival in relation to VEGFR-1 and VEGFR-2 expression in our cohort of 86 CRC patients stage III-IV only (Pancione et al. unpublished data). (d) Schematic drawing of the proposed mechanism(s) involved in metastasis-promoting actions of VEGFR-1 and VEGFR-2, respectively. VEGFR-1, but not VEGFR-2, is expressed in a variety of stromal cells and appears synergized with TME in the evolution of premetastatic niche and cancer cell migration. Aflibercept targeting PlGF/VEGFR-1 axis can reduce the induction of an angiogenic rescue program and inhibit immune cells recruitment and metastatic progression. The value is reported in each graph. Cum. (cumulative), Met. (metastases), Neg. (negative), Pos. (positive), and Tum. (tumor).
