VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche.

The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice.

Oncolytic herpes simplex virus-1 mutant expressing green fluorescent protein can detect and treat peritoneal cancer.

NV1066 is a herpes simplex virus-1 (HSV-1) oncolytic mutant that contains the gene for enhanced green fluorescent protein (EGFP). We sought to determine (1) whether NV1066 is effective against human peritoneal cancer, (2) whether EGFP is detectable in an animal model of gastric cancer, and (3) whether EGFP expression can be used to assess oncolytic therapy in a minimally invasive, laparoscopic system. The current study demonstrates that NV1066 is cytotoxic to OCUM human gastric cancer cells in vitro and in an in vivo model of disseminated peritoneal gastric cancer.