Detection of endogenously circulating mesenchymal stem cells in human cancer patients.

Abstract

Mesenchymal stem cells (MSCs) can play a vital role in tumor progression and anticancer therapy response, as demonstrated by various in vitro and in vivo model systems. Their ability to home to developing tumors and modulate the tumor microenvironment, by suppressing T-cell responses and contributing to the tumor stroma, is suggested to have a significant impact on disease progression, metastasis formation, and therapy response. Most evidence, however, is derived from artificial models using exogenously administered MSCs. The contribution of endogenous MSCs to tumor progression is currently unclear. Furthermore, few studies have been conducted in humans. A prospective biomarker study was therefore undertaken in 40 human cancer patients and 10 healthy controls of similar age, aimed at (i) exploring and quantifying circulating MSC levels in healthy volunteers and patients with advanced malignancies, (ii) determining the variability of MSC levels between healthy volunteers and cancer patients with different histologic tumor types, and (iii) exploring biomarkers associated with MSC levels. Significantly increased levels of circulating MSC-like cells were observed in cancer patients when compared to healthy individuals (1.72 fold difference, 95% CI 1.03-2.81%, p = 0.03). In addition, prior systemic therapy was associated with a significant increase in MSC-like cells (1.73 fold difference, 95% CI 1.02-2.95, p = 0.04). These results indicate that the amount of endogenously circulating MSCs in humans is increased in response to cancer, and that systemic anticancer treatment can influence MSC levels. Further research is needed to determine whether MSCs have a predictive value.