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Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype.

Pang LY, Cervantes-Arias A, Else RW, Argyle DJ - Cancers (Basel) (2011)

Bottom Line: Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs.Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype.Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

View Article: PubMed Central - PubMed

Affiliation: Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. lisa.pang@ed.ac.uk.

ABSTRACT
Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

No MeSH data available.


Related in: MedlinePlus

TGFβ treated cells show an increased tumorsphere forming ability compared to untreated cells. Tumorspheres resulted less frequently from untreated cells (A), compared to cells treated with 10 ng/ml TGFβ (B). The resultant number of spherical colonies were counted (★ p < 0.001; ★ ★ p < 0.001; ★ ★ ★ p < 0.01) (C).
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f5-cancers-03-01744: TGFβ treated cells show an increased tumorsphere forming ability compared to untreated cells. Tumorspheres resulted less frequently from untreated cells (A), compared to cells treated with 10 ng/ml TGFβ (B). The resultant number of spherical colonies were counted (★ p < 0.001; ★ ★ p < 0.001; ★ ★ ★ p < 0.01) (C).

Mentions: EMT activation is proposed to enrich the proportion of cancer stem cells with a given cell population. Therefore we tested the ability of TGFβ treated cells to form tumorspheres when grown in suspension cultures, as an in vitro measure of cancer stem cell activity. TGFβ treated cells formed large clearly identifiable tumorspheres after 7 days in culture (Figure 5A) and showed an ∼8-fold increase in tumorsphere forming ability relative to untreated cells (Figure 5B). This data indicates that canine mammary carcinoma cells induced to undergo an EMT by TGFβ contained a significantly greater proportion of cells with a CSC-like phenotype compared to control cells.


Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype.

Pang LY, Cervantes-Arias A, Else RW, Argyle DJ - Cancers (Basel) (2011)

TGFβ treated cells show an increased tumorsphere forming ability compared to untreated cells. Tumorspheres resulted less frequently from untreated cells (A), compared to cells treated with 10 ng/ml TGFβ (B). The resultant number of spherical colonies were counted (★ p < 0.001; ★ ★ p < 0.001; ★ ★ ★ p < 0.01) (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757388&req=5

f5-cancers-03-01744: TGFβ treated cells show an increased tumorsphere forming ability compared to untreated cells. Tumorspheres resulted less frequently from untreated cells (A), compared to cells treated with 10 ng/ml TGFβ (B). The resultant number of spherical colonies were counted (★ p < 0.001; ★ ★ p < 0.001; ★ ★ ★ p < 0.01) (C).
Mentions: EMT activation is proposed to enrich the proportion of cancer stem cells with a given cell population. Therefore we tested the ability of TGFβ treated cells to form tumorspheres when grown in suspension cultures, as an in vitro measure of cancer stem cell activity. TGFβ treated cells formed large clearly identifiable tumorspheres after 7 days in culture (Figure 5A) and showed an ∼8-fold increase in tumorsphere forming ability relative to untreated cells (Figure 5B). This data indicates that canine mammary carcinoma cells induced to undergo an EMT by TGFβ contained a significantly greater proportion of cells with a CSC-like phenotype compared to control cells.

Bottom Line: Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs.Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype.Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

View Article: PubMed Central - PubMed

Affiliation: Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. lisa.pang@ed.ac.uk.

ABSTRACT
Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

No MeSH data available.


Related in: MedlinePlus