Abstract 2498: Tumorspheres cultured from circulating epithelial tumor cells (CETCs) overexpress stem cell markers in patients with solid cancers

32 Background: Even after the complete resection of a malignant tumor the menace remains, that cells that have dissociated from the tumor might resettle in distant organs and grow into life-threatening metastases. Therefore we have developed an approach (maintrac) to detect and monitor the circulating tumor suspect epithelial cells in blood. However, the question arises whether these cells have the potential to grow into metastases. Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, the cells from the pellet, containing the white blood cells together with the putative tumor cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14 and 21 days the cultured cells were stained with anti-EpCAM antibody and inspected for the appearance of epithelial antigen positive spheroids. Results: Peripherally circulating cells from patients with malignant tumors in different stages of disease were analyzed for the presence of circulating epithelial tumor suspect cells and the frequencies of tumorspheres. Tumorspheres could so far be grown from 79% of 36 patients in whom more than 1700/ml epithelial tumor suspect cells were detected. Numbers of tumorspheres varied from 1 to 29 /ml and correlated with the aggressiveness of the tumor. Surprsingly the numbers were highest in patients who had not yet received any systemic therapy after surgery. The size of the spheres increased from day 7 to day 21. The spheres were negative for CD24 and positive for CD44. They highly expressed ALDH1 and thus exhibited typical features of stem cells. Conclusions: Here, we demonstrate that the tumor suspect cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres. The frequency and growth potential of cells capable of forming spheres seems to be dependent from the properties of the primary tumor. The possibility to grow tumorspheres from peripherally circulating tumor cells may open up a new field, where the relevant cells with stem cell properties from individual patients can now be specifically analysed further for genetic endowment, transcriptional activity, heterogeneity and stem cell markers.

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Expression of Epithelial Mesenchymal Transition and Cancer Stem Cell Markers in Circulating Tumor Cells

Advances in Experimental Medicine and Biology - Isolation and Molecular Characterization of Circulating Tumor Cells ◽

10.1007/978-3-319-55947-6_11 ◽

2017 ◽

pp. 205-228 ◽

Cited By ~ 14

Author(s):

Stefan Werner ◽

Arnulf Stenzl ◽

Klaus Pantel ◽

Tilman Todenhöfer

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Epithelial Mesenchymal Transition ◽

Stem Cell Markers ◽

Mesenchymal Transition ◽

Cell Markers ◽

Cancer Stem Cell Markers

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Sca1+ murine pituitary adenoma cells show tumor-growth advantage

Endocrine Related Cancer ◽

10.1530/erc-13-0229 ◽

2014 ◽

Vol 21 (2) ◽

pp. 203-216 ◽

Cited By ~ 16

Author(s):

Ines Donangelo ◽

Song-Guang Ren ◽

Tamar Eigler ◽

Clive Svendsen ◽

Shlomo Melmed

Keyword(s):

Stem Cell ◽

Growth Factor ◽

Brain Tumors ◽

Tumor Growth ◽

Tumor Cells ◽

Cell Population ◽

Pituitary Adenomas ◽

Pituitary Tumor ◽

Stem Cell Markers ◽

Cell Markers

The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. In this study, we investigated whether the cells within pituitary adenomas that spontaneously develop in Rb+/− mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, and CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1+ cell population that showed increased sphere formation potential, lower mRNA hormone expression, higher expression of stem cell markers (Notch1, Sox2, and Nestin), and increased proliferation rates. When transplanted into non-obese diabetic-severe combined immunodeficiency gamma mice brains, Sca1+ pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 (100%) vs 7/12 (54%) of mice transplanted with Sca1+ and Sca1− cells respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that tumors derived from Sca1+ pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1+ cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor-proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells.

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Cancer stem cells and their detection using specific cancer stem cell markers- a new strategy for cancer therapies

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.17.3.0357 ◽

2021 ◽

Vol 17 (3) ◽

pp. 094-099

Author(s):

Khalida I. Noel ◽

Rana M. Raoof ◽

Nibras H. Khamees

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

Tumor Cells ◽

Cancer Tissue ◽

Stem Cell Markers ◽

Cancer Therapies ◽

Cell Markers ◽

Cancer Stem Cell Markers

Background: In the previous theories of cancer, they considered that cancer was a homogeneous which mean that the tumor had only tumor cells and for this reason the treatment for any tumor directed to kill these tumor cells. But, with rising of the metastatic cases of cancer patients, another theory have been raised, that the cancer is a heterogeneous disease which composed of tumor cells that previously the chemotherapy and other cancer therapies directed toward them, in addition there is another group of cells, called cancer stem cells (CSCs), these are more aggressive than the tumor cells that can force the poor microenvironment of the cancer tissue and survive and also they are undifferentiated cells so can undergo mitosis to produce more tumor cells and another group of cancer stem cells in contrast to the tumor cells, which considered a post mitotic and not divided. Objective: Demonstrate some of cancer stem cell markers that considered an important indicators of early cancer development and lately to detect cases of metastasis. Conclusion: The theory of the presence of cancer stem cells is more acceptable and applicable and so the cancer therapy must be directed to these groups of cancer stem cells.

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Growth of tumorspheres from peripherally circulating tumor cells.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.30_suppl.2 ◽

2012 ◽

Vol 30 (30_suppl) ◽

pp. 2-2

Author(s):

Dorothea Zimon ◽

Monica Pizon ◽

Ulrich A. Pachmann ◽

Katharina Pachmann

Keyword(s):

Colon Cancer ◽

Stem Cell ◽

Epithelial Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

White Blood Cells ◽

Growth Potential ◽

Stem Cell Markers ◽

Metastatic Colon Cancer ◽

Epithelial Tumor

2 Background: Even after the complete resection of a malignant tumor the menace remains, that cells that have dissociated from the tumor might resettle in distant organs and grow into life-threatening metastases. Therefore we have developed an approach (maintrac) to detect and monitor the circulating tumor suspect epithelial cells in blood. However, the question arises whether these cells have the potential to grow into metastases. Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, the cells from the pellet, containing the white blood cells together with the putative tumor cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14, and 21 days the cultured cells were stained with anti-EpCAM antibody and inspected for the appearance of epithelial antigen positive spheroids. Results: Peripherally circulating cells from patients with malignant tumors in different stages of disease were analyzed for the presence of circulating epithelial tumor suspect cells and the frequencies of tumorspheres. Tumorspheres could so far be grown from all of 20 patients in whom more than 2000/ml epithelial tumor suspect cells were detected. Fractions of tumorspheres varied from less than 1% of the epithelial tumor suspect cells in patients with primary breast cancer to up to 70% in a patient with an aggressively growing metastatic colon cancer. The size of the spheres increased from day 7 to day 21 but already had reached the size of day 21 colonies after seven days in the patient with the metastatic colon cancer. Conclusions: Here, we demonstrate that the tumor suspect cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres. The frequency and growth potential of cells capable of forming spheres seems to be dependent from the properties of the primary tumor. The possibility to grow tumorspheres from peripherally circulating tumor cells may open up a new field, where the relevant cells with stem cell properties from individual patients can now be specifically analysed further for genetic endowment, transcriptional activity, heterogeneity, and stem cell markers.

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