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Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer.

Pizon M, Zimon D, Carl S, Pachmann U, Pachmann K, Camara O - Ecancermedicalscience (2013)

Bottom Line: Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs).Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery.Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

View Article: PubMed Central - PubMed

Affiliation: Transfusion Center Bayreuth D-95448, Germany.

ABSTRACT

Background: The detection of tumour cells circulating in the peripheral blood of patients with breast cancer is a sign that cells have been able to leave the primary tumour and survive in the circulation. However, in order to form metastases, they require additional properties such as the ability to adhere, self-renew, and grow. Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs).

Patients and methods: Between ten and 50 circulating epithelial antigen-positive cells detected by the Maintrac approach were selected randomly from each of 20 patients with breast cancer before and after surgery and were isolated using automated capillary aspiration and deposited individually onto slides for expression profiling. In addition, the circulating tumour cells were cultured without isolation among the white blood cells from 39 patients with breast cancer in different stages of disease using culture methods favouring growth of epithelial cells.

Results: Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery. Tumour spheres from circulating cells of 39 patients with different stages of breast cancer were grown without previous isolation in a fraction increasing with the aggressivity of the tumour.

Summary: Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

No MeSH data available.


Related in: MedlinePlus

The number of tumour spheres per millilitre of blood from 39 breast cancer patients in different stages of disease at 21 days of culture. The differences were significant between patients with stage I tumours versus triple-negative tumours (p = 0.033), stage II–III tumours prior to chemotherapy (p= 0.025), and metastatic disease (p= 0.015).
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figure5: The number of tumour spheres per millilitre of blood from 39 breast cancer patients in different stages of disease at 21 days of culture. The differences were significant between patients with stage I tumours versus triple-negative tumours (p = 0.033), stage II–III tumours prior to chemotherapy (p= 0.025), and metastatic disease (p= 0.015).

Mentions: The number of spheres was determined from 1 mL of blood from 39 breast cancer patients. The numbers of spheres varied from 0–29/mL. The distribution of sphere numbers from patients with breast cancer at different stages is shown in Figure 5. Surprisingly, the number of sphere-forming cells was widely distributed in patients with ductal carcinoma in situ (DCIS), whereas sphere-forming cells were absent in all three patients with stage I tumours. Patients with triple-negative breast cancer and patients with metastatic disease exhibited significantly higher levels of sphere-forming cells than patients with stage I tumours (p = 0.033 and 0.015, respectively) and somewhat higher levels than patients with stage II–III tumours treated according to the guidelines. Most importantly, patients with non-metastatic tumours who had been operated on and not yet received any chemotherapy exhibited almost the same high numbers of sphere-forming cells (p = 0.025) as those found in patients with metastatic disease.


Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer.

Pizon M, Zimon D, Carl S, Pachmann U, Pachmann K, Camara O - Ecancermedicalscience (2013)

The number of tumour spheres per millilitre of blood from 39 breast cancer patients in different stages of disease at 21 days of culture. The differences were significant between patients with stage I tumours versus triple-negative tumours (p = 0.033), stage II–III tumours prior to chemotherapy (p= 0.025), and metastatic disease (p= 0.015).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750196&req=5

figure5: The number of tumour spheres per millilitre of blood from 39 breast cancer patients in different stages of disease at 21 days of culture. The differences were significant between patients with stage I tumours versus triple-negative tumours (p = 0.033), stage II–III tumours prior to chemotherapy (p= 0.025), and metastatic disease (p= 0.015).
Mentions: The number of spheres was determined from 1 mL of blood from 39 breast cancer patients. The numbers of spheres varied from 0–29/mL. The distribution of sphere numbers from patients with breast cancer at different stages is shown in Figure 5. Surprisingly, the number of sphere-forming cells was widely distributed in patients with ductal carcinoma in situ (DCIS), whereas sphere-forming cells were absent in all three patients with stage I tumours. Patients with triple-negative breast cancer and patients with metastatic disease exhibited significantly higher levels of sphere-forming cells than patients with stage I tumours (p = 0.033 and 0.015, respectively) and somewhat higher levels than patients with stage II–III tumours treated according to the guidelines. Most importantly, patients with non-metastatic tumours who had been operated on and not yet received any chemotherapy exhibited almost the same high numbers of sphere-forming cells (p = 0.025) as those found in patients with metastatic disease.

Bottom Line: Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs).Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery.Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

View Article: PubMed Central - PubMed

Affiliation: Transfusion Center Bayreuth D-95448, Germany.

ABSTRACT

Background: The detection of tumour cells circulating in the peripheral blood of patients with breast cancer is a sign that cells have been able to leave the primary tumour and survive in the circulation. However, in order to form metastases, they require additional properties such as the ability to adhere, self-renew, and grow. Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac(®) approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs).

Patients and methods: Between ten and 50 circulating epithelial antigen-positive cells detected by the Maintrac approach were selected randomly from each of 20 patients with breast cancer before and after surgery and were isolated using automated capillary aspiration and deposited individually onto slides for expression profiling. In addition, the circulating tumour cells were cultured without isolation among the white blood cells from 39 patients with breast cancer in different stages of disease using culture methods favouring growth of epithelial cells.

Results: Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%-20% of the cells were found to be positive for mRNA of these genes after surgery. Tumour spheres from circulating cells of 39 patients with different stages of breast cancer were grown without previous isolation in a fraction increasing with the aggressivity of the tumour.

Summary: Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

No MeSH data available.


Related in: MedlinePlus