Abstract
BackgroundUterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. However, little is known about CSCs and their associated-markers in ULMS. We aimed to characterize and identify a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cell line.MethodsSK-UT-1 cells were sphere-forming cultured in vitro. We also sorted the CD133+ cells derived from SK-UT-1 cell line by immunomagnetic beads. CD133+ subpopulation and apoptotic cells were detected by flow cytometry. Self-renewal and anchorage-independent growth capabilities were examined using sphere and colony formation assays. The tumorigenicity of the fourth-passage spheres and parental SK-UT-1 cells was used by mouse xenograft model in vivo. Cell proliferation ability and sensitivity to doxorubicin (DXR) were assessed by CCK-8 assay. Cell migration and invasion were tested by wound healing assay or Transwell migration and invasion assays. Expressions of CSC-related marker were analyzed by Western blotting.ResultsThe fourth-passage spheres were defined as a CD133+ cell population, which was accompanied by increase of sphere and colony forming rate, migration and invasion abilities, as well as drug-resistant properties in vitro. Moreover, the fourth-passage spheres showed a stronger tumorigenic potential in vivo. CD133+ cell population sorted from SK-UT-1 line showed an increased ability in sphere and colony formation, proliferation, migration, invasion, resistance to apoptosis after treatment with doxorubicin (DXR) compared with CD133− cell population. The expression levels of CSCs-related markers (e.g., CD44, ALDH1,BMI1, and Nanog), were significantly elevated in CD133+ cells compared with those in CD133− cells.ConclusionsCollectively, our findings indicated that CD133 may be a significant marker for cancer stem-like cells, and it may be a potential therapeutic target for human ULMS.
Highlights
Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus
Sphere‐forming culture could enrich CD133+ cells derived from SK‐UT‐1 cells Sphere-forming culture is often used to enrich Cancer stem cells (CSCs) or cancer stem-like cells [18, 19]
Various types of cancer cells have been found to contain a subset of CSCs or cancer stem-like cells, while little is known about how can we obtain the cancer stem-like cells using an enrichment approach and which molecule can be served as cancer stem cell-surface markers in ULMS
Summary
Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. Uterine leiomyosarcoma (ULMS) is an aggressive malignancy characterized by its early metastasis, high rates of recurrence, and poor prognosis [1]. The recurrence rate of ULMS remains as high as 70 % [2, Gao et al Cancer Cell Int (2021) 21:157. CSCs are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure [5]. These cells highly express surface markers similar to those of normal stem cells, including CD44, CD24, and CD133 [6]. Little is known about CSCs and their associated-markers in ULMS
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