PyMT-1099, a versatile murine cell model for EMT in breast cancer.
Meera SaxenaRavi Kiran Reddy KalathurMelanie NeutznerGerhard ChristoforiPublished in: Scientific reports (2018)
An epithelial-mesenchymal transition (EMT) has been implicated in cancer metastasis, drug resistance, and in conferring stem cell-like traits to cancer cells. Most studies investigating EMT in cancer have either utilized immortalized or cancer cell lines that are already primed to undergo an EMT and do not adequately represent a fully differentiated epithelial state in the absence of an EMT induction. Hence, model systems are required which recapitulate all stages of EMT in cancer cells. Here, we report the derivation and characterization of epithelial PyMT-1099 cancer cells from the MMTV-PyMT mouse model of breast cancer. We demonstrate that PyMT-1099 cells undergo an EMT upon TGFβ treatment, while upon TGFβ withdrawal they go through a mesenchymal-epithelial transition (MET), as assessed by changes in cell morphology and marker expression and comparable to normal murine mammary gland NMuMG cells. However, in contrast to NMuMG cells, PyMT-1099 cells show an increase in cell migration and are highly tumorigenic and metastatic when transplanted into immunocompromised mice. Finally, we report cancer cell-specific changes in gene expression during EMT of PyMT-1099 cells not found in non-transformed NMuMG cells. Thus, PyMT-1099 cells are a versatile tool to study breast cancer-associated EMT and MET in vitro and in vivo.
Keyphrases
- epithelial mesenchymal transition
- induced apoptosis
- cell cycle arrest
- gene expression
- transforming growth factor
- signaling pathway
- mouse model
- oxidative stress
- small cell lung cancer
- magnetic resonance
- endoplasmic reticulum stress
- magnetic resonance imaging
- squamous cell carcinoma
- type diabetes
- poor prognosis
- squamous cell
- cell therapy
- tyrosine kinase
- skeletal muscle
- computed tomography
- pi k akt
- bone marrow
- long non coding rna
- lymph node metastasis
- contrast enhanced
- replacement therapy