Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild type counterparts expressing all isoforms (fs120, fs164, fs188 or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 versus fs188/WT); fs120 cells also produced more lung colonies than fs188 cells when injected intravenously. Metastasis from subcutaneous fs120 tumors was more sensitive than fs188 to treatment with the anti-VEGFA antibody B20-4.1.1. Despite elevated plasma levels of VEGFA in fs120 tumor-bearing mice and a dependence on VEGF receptor 1 activity for metastasis to the lung, B20-4.1.1 did not affect survival in the lung on intravenous injection. B20-4.1.1 inhibited subcutaneous tumor growth and decreased vascular density in both fs120 and fs188 tumors. However, migration of fs120, but not fs188 cells in vitro was inhibited by B20-4.1.1. The greater survival of fs120 cells in the lung was associated with VEGFR1-dependent accumulation of CD11b positive myeloid cells and higher expression of the VEGFR1 ligand, PlGF2, by the fs120 cells in vitro and in the plasma and lungs of fs120 tumor-bearing mice. We conclude that soluble VEGFA isoform expression increases fibrosarcoma metastasis through multiple mechanisms that vary in their sensitivity to anti-VEGF/VEGFR inhibition, with VEGFA-targeted therapy suppressing metastasis through effects on the primary tumor rather than the metastatic site
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nI9Ffn
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
A study using a new computer-aided detection (CAD) algorithm found breast cancers... Read more on AuntMinnieEurope.com Related Reading: ...
-
This study analyzes 24 climate extreme indices over North Thailand using observed data for daily maximum and minimum temperatures and total ...
-
Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a multisystem autoimmune disease affecting mainly microscopic bl...
-
: local control, functional, and esthetic outcomes p. 82 Deepak Balasubramanian, Narayana Subramaniam, Sherry Peter, Latha Rao, Pramod Sub...
-
Background. Peritoneal Carcinomatosis Index (PCI) is a widely established scoring system that describes disease burden in isolated colorecta...
-
Within the framework of augmented version of superfield formalism, we derive the superspace unitary operator and show its usefulness in the ...
-
: Intent to treat analysis p. 78 Sajith Babu Thavarool, Amit Tyagi, KN Harsha, Bhushan Kathuria, Nagendra Kadappa, Sithara Aravind, KM Asw...
-
Objective To examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI...
-
This study proposes an improved metabolism grey model [IMGM] to predict small samples with a singular datum, which is a common phenomenon in...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου