journal contribution posted on 2023-03-31, 21:10 authored by Aida Freire Valls, Karl Knipper, Evangelia Giannakouri, Víctor Sarachaga, Sascha Hinterkopf, Michael Wuehrl, Ying Shen, Praveenkumar Radhakrishnan, Johannes Klose, Alexis Ulrich, Martin Schneider, Hellmut G. Augustin, Carmen Ruiz de Almodovar, Thomas Schmidt
Supplementary methods, tables and supplementary figure legends Table S1. Patient characteristics. Table S2. Kind of neo-adjuvant therapy from LM patients included in the analysis of blood samples by flow cytometry. Table S3. Primer list used for qRT-PCR. Table S4. Association of circulating CD11b+ CD68+ VEGFR1+ cells with clinicopathologic variables in patients with liver metastasis of colorectal cancer. Table S5. Univariate analysis of factors associated with progression-free survival in patients with liver metastasis of CRC. Table S6. Multivariate analysis of factors associated with circulating VEGFR1+ macrophages and progression-free survival in LM patients.
Jung Foundation for Science and Research
Heidelberg Foundation of Surgery
ARTICLE ABSTRACTTo investigate the clinical relevance of macrophages in liver metastasis of colorectal cancer and their influence on angiogenesis and patient survival. Moreover to evaluate specific blood monocytes as markers of disease recurrence.Experimental design: In a mouse model with spontaneous liver metastasis, the angiogenic characteristics of tumor- and metastasis (MAM)-associated macrophages were evaluated. Macrophages and the vasculature from 130 primary tumor (pTU) and 123 patients with liver metastasis were assessed. In vivo and in human samples, the clinical relevance of macrophage VEGFR1 expression was analyzed. Blood samples from patients (n = 157, 80 pTU and 77 liver metastasis) were analyzed for assessing VEGFR1-positive (VEGFR1+) cells as suitable biomarkers of disease recurrence.
The number of macrophages positively correlated with vascularization in metastasis. Both in the murine model as well as in primary isolated human cells, a subpopulation of MAMs expressing VEGFR1 were found highly angiogenic. While VEGFR1 expression in pTU patients did not predict prognosis; high percentage of VEGFR1+ cells in liver metastasis was associated with worse patient outcome. Interestingly, VEGFR1+-circulating monocytes in blood samples from patients with liver metastasis not only predicted progression but also site of recurrence.
Our findings identify a new subset of proangiogenic VEGFR1+ MAMs in colorectal cancer that support metastatic growth and may become a liquid biomarker to predict disease recurrence in the liver.