Morphine Treated Mesenchymal Stem Cells Condi-tioned Medium Enriches Cancer Stem Cell Populations of Murine Mammary Tumor 4T1 Cell Line

Background: Mesenchymal stem cells (MSCs) are a group of non-hematopoietic adult stem cells with capacity for self-renewal and differentiation. They are an important component of the tumor microenvironment and recruited by cancer cells to similarly promote tumor growth and progression. Morphine, an opiate-based agent is widely used for management of se-vere pain associated with cancer metastasis. Many tumors, in-cluding breast cancer, consists of undifferentiated slow-cycling cells with self-renewing capacity which maintain tumor growth called cancer stem cells (CSCs). These cells are identified with CD44+ /CD24- cell surface markers. An increasing amount of evidences indicate a possibility that morphine causes immuno-suppression on the hosts. This survey was designed to deter-mine the effect of morphine on the interaction of MSCs and 4T1 cells that may promotes CSCs populations.Materials and Methods: MSC was isolated by flashing the Tib-ia and femur bones of mice. After 14 days, MSCs were incubated for 24 h with 0 and 10 µM of Morphine. Then cells were cultured without serum for 24h and the conditioned medium (CM) was isolated. 4T1 cells were incubated for 2 weeks in a medium with isolated CM (50%) and FBS. The medium was changed every 2 or 3 days. Cells were then harvested and incubated with antibod-ies against CD44 and CD24 for detection of CSCs.Results: Flow cytometry analysis indicated that the CM of MSCs treated with 10 µM of morphine could significantly in-creases the number of CSCs within murine mammary tumor 4T1 cell line. Percentage of 10 µM is almost two times higher than percentage of control group.Conclusion: This data clearly showed that treatment with CM of morphine treated MSCs results in enrichment of cancer stem cell populations within 4T1 cells.

کلیدواژه ها:

Mesenchymal Stem Cells ، Conditioned Medium ، Morphine ، 4T1 Cell Line ، Cancer Stem Cells