Nanomolar concentration of blood-soluble drag-reducing polymer inhibits experimental metastasis of human breast cancer cells

Abstract

Metastasis is the leading cause of cancer mortality. Extravasation of cancer cells is a critical step of metastasis. We report a novel proof-of-concept study that investigated whether non-toxic blood-soluble chemical agents capable of rheological modification of the near-vessel-wall blood flow can reduce extravasation of tumor cells and subsequent development of metastasis. Using an experimental metastasis model, we demonstrated that systemic administration of nanomolar concentrations of so-called drag-reducing polymer dramatically impeded extravasation and development of pulmonary metastasis of breast cancer cells in mice. This is the first proof-of-principle study to directly demonstrate physical/rheological, as opposed to chemical, way to prevent cancer cells from extravasation and developing metastasis and, thus, it opens the possibility of a new direction of adjuvant interventional approach in cancer.

Keywords:

• breast cancer
• metastasis
• extravasation
• hemodynamics
• drag-reducing polymer
• blood cell traffic
• microvessels

Acknowledgments

This study was supported by grants from the Congressionally Directed Medical Research Program of the Department of Defense (W81XWH-11-1-0122) and National Institute of Health (R01 CA108607) to PR.

Disclosure

The authors report no conflicts of interest in this work.