The Effect of Chemotherapeutic Agents on Tumor Vasculature in Subcutaneous and Orthotopic Human Tumor Xenografts

BMC Cancer. 2015 Mar 10;15:112. doi: 10.1186/s12885-015-1091-6.

Abstract

Background: The growth of solid tumors and their regrowth after treatment is dependent upon functional tumor vasculature. Some chemotherapeutic agents have shown anti-angiogenic properties but there are limited studies of the effect of chemotherapy on tumor vasculature. Here we investigate the effect of paclitaxel, 5-fluorouracil (5-FU) and doxorubicin on tumor vasculature in subcutaneous and orthotopic xenografts in mice.

Methods: The vascular density and percentage of functional blood vessels were evaluated in subcutaneous A431 human vulvar cancer xenografts, and in subcutaneous and orthotopic MCF-7 human breast cancer xenografts, following single doses of paclitaxel, 5-FU or doxorubicin.

Results: There was no significant difference in total (CD31+) blood vessels between untreated ectopic and orthotopic MCF-7 tumors, but there was a significantly lower proportion of functional blood vessels in orthotopic tumors. After paclitaxel treatment, there was a decrease in functional tumor vasculature in A431 subcutaneous xenografts, followed by a subsequent rebound. There was a significant decrease in total vascular density on day 12 in A431 tumors following 5-FU or doxorubicin treatment, but no change in the percentage of functional vessels. An increase in functional blood vessels or percentage of functional vasculature was noted in MCF-7 subcutaneous and orthotopic xenografts following chemotherapy treatment.

Conclusions: There are differences in the vasculature and microenvironment of ectopic and orthotopic xenografts in mice. Anti-tumor effects of chemotherapy may be due, in part, to effects on tumor vasculature and may vary in different tumor models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers