Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging.

Abstract

BACKGROUND:

We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam® color-coded imaging assay.

MATERIALS AND METHODS:

Gelfoam® was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam®, control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small-animal imaging system and confocal fluorescence microscopy.

RESULTS:

Nascent blood vessels expressing ND-GFP extended into the Gelfoam® over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28.

CONCLUSION:

The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma.

• Authors: Tasuku Kiyuna, Yasunori Tome, Fuminari Uehara, Takashi Murakami, Yong Zhang, Ming Zhao, Fuminori Kanaya, Robert M Hoffman
• Journal: Anticancer research (Anticancer Res) Vol. 38 Issue 1 Pg. 159-164 (01 2018) ISSN: 1791-7530 [Electronic] Greece
• PMID: 29277768 (Publication Type: Journal Article)
• Copyright: Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Topics

• Animals
• Bone Neoplasms (blood supply, pathology, therapy)
• Cell Line, Tumor
• Female
• Humans
• Mice, Nude
• Mice, Transgenic
• Neovascularization, Pathologic (therapy)
• Osteosarcoma (blood supply, pathology, therapy)
• Salmonella typhimurium