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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

Putative cancer stem cells exhibit mesenchymal characteristics. Tumorspheres derived from the REM134 canine mammary carcinoma cell line express mesenchymal markers (A). Invasive capacity was assayed using a collagen-based cell invasion assay kit. Invading cells are stained (C) and quantified by colorimetric measurement at 560 nm (★ p < 0.008) (B).
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f3-cancers-03-01744: Putative cancer stem cells exhibit mesenchymal characteristics. Tumorspheres derived from the REM134 canine mammary carcinoma cell line express mesenchymal markers (A). Invasive capacity was assayed using a collagen-based cell invasion assay kit. Invading cells are stained (C) and quantified by colorimetric measurement at 560 nm (★ p < 0.008) (B).

Mentions: The metastatic process involves cell detachment from the extracellular matrix, migration from the tumor microenvironment and subsequent invasion and attachment at a secondary site within the body. Although the mechanisms underlying tumor cell invasion remain incompletely understood, EMT has been implicated by promoting loss of contact inhibition, increased cell motility and enhanced invasiveness [26,38]. Here we examined the expression of well-known epithelial markers (E-cadherin and β-catenin) and mesenchymal markers (Fibronectin and Vimentin) [39]. Tumorspheres were dissociated into single cells and compared to parental cells. Western blot analysis showed that the expression of E-cadherin and β-catenin was significantly decreased, whereas that of Fibronectin and Vimentin was significantly increased in tumorspheres compared to parental adherent cells (Figure 3A). Therefore tumorspheres that exhibit increased resistance to ionizing radiation and chemotherapy, have a mesenchymal phenotype.


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)

Putative cancer stem cells exhibit mesenchymal characteristics. Tumorspheres derived from the REM134 canine mammary carcinoma cell line express mesenchymal markers (A). Invasive capacity was assayed using a collagen-based cell invasion assay kit. Invading cells are stained (C) and quantified by colorimetric measurement at 560 nm (★ p < 0.008) (B).
© Copyright Policy
Related In: Results  -  Collection

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

f3-cancers-03-01744: Putative cancer stem cells exhibit mesenchymal characteristics. Tumorspheres derived from the REM134 canine mammary carcinoma cell line express mesenchymal markers (A). Invasive capacity was assayed using a collagen-based cell invasion assay kit. Invading cells are stained (C) and quantified by colorimetric measurement at 560 nm (★ p < 0.008) (B).
Mentions: The metastatic process involves cell detachment from the extracellular matrix, migration from the tumor microenvironment and subsequent invasion and attachment at a secondary site within the body. Although the mechanisms underlying tumor cell invasion remain incompletely understood, EMT has been implicated by promoting loss of contact inhibition, increased cell motility and enhanced invasiveness [26,38]. Here we examined the expression of well-known epithelial markers (E-cadherin and β-catenin) and mesenchymal markers (Fibronectin and Vimentin) [39]. Tumorspheres were dissociated into single cells and compared to parental cells. Western blot analysis showed that the expression of E-cadherin and β-catenin was significantly decreased, whereas that of Fibronectin and Vimentin was significantly increased in tumorspheres compared to parental adherent cells (Figure 3A). Therefore tumorspheres that exhibit increased resistance to ionizing radiation and chemotherapy, have a mesenchymal phenotype.

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