Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

Abstract

Tumors are composed of heterogeneous populations of cells including tumor-initiating cells (TICs) and metastatic precursors. While the origin of these cells is unknown, there is evidence that tumor cells can transdifferentiate from an epithelial to a mesenchymal phenotype, a property referred to as epithelial-to-mesenchymal transition (EMT). This cellular plasticity may explain the heterogeneous nature of tumors and differences in the tumorigenic and invasive properties of cells. Understanding the origin of these cells and the contribution of external factors that influence the acquisition of cellular properties is critical for the development of therapeutics to eradicate cancer. In this study, we show that primary murine tumor cells harvested from FVB/N Tg (MMTV/Neu) spontaneous mammary tumors possess differentiation plasticity and can be enriched to be epithelial or mesenchymal-like using selected culture media conditions, and we show evidence of EMT in a clonal population of primary epithelial tumor cells when cultured in fibroblast growth factor-1 (FGF-1) or transforming growth factor-β (TGF-β). We also determined that in contrast to the identification of mesenchymal-like tumor cells as TICs in orthotopic xenograph models of tumorigenicity, epithelial-enriched

A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential

“…Many have shown a capacity for multilineage differentiation into tumor-supporting vascular and stromal cells and endothelium24252627. The current study is the first to demonstrate a capacity for mesothelioma tumor cell differentiation to the osteoblast lineage, providing further evidence for a mesothelial progenitor origin for the osseous elements found within a subset of mesothelioma tumors.…”

Clinicopathological significance of fibroblast growth factor 1 in non–small cell lung cancer

“…Besides the proangiogenic effect of FGF1 in tumor cells, FGF1 has been confirmed to increase the proliferation and survival of some cancer cells, including breast cancer [30], head and neck cancer [31], and ovarian cancer [16]. Besides, FGF1 has been found to promote epithelialto-mesenchymal transition [32,33] and induce the production of proteases, such as matrix metalloproteinase (MMP) 1 and MMP9 [34,35], facilitating cancer cell invasion and metastasis. Although we did not uncover the precise mechanisms underlying FGF1 role on prognosis in NSCLC patients, our findings indicated that FGF1 may at least partly accelerate tumor progression by increasing NSCLC angiogenesis and it may be used as a poor prognostic marker for NSCLC patients.…”

E-cadherin re-expression showsin vivoevidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells

“…Cells were sorted from single cell suspensions by flow cytometry based on neu and CD24 expression to separate epithelial and mesenchymal-like cells from the tumor mass. Epithelial tumor cells were enriched in the neu hi CD24 hi population and mesenchymal-like cells were enriched in the neu low CD24 low cell population [7]. Two clonal epithelial cell lines (E1 and E2) and 2 clonal mesenchymal-like cell lines (M1 and M2) were obtained by limiting dilution cell culture.…”

“…It is known that EMT can be induced in tumor cell lines by external factors. Some of these include transforming growth factor beta (TGF-β), [1], hepatocyte growth factor (HGF) [2], epidermal growth factors (EGF) [3], insulin-like growth factors (IGF) [4], and fibroblastic growth factor (FGF) [5, 7]. There is also evidence that mesenchymal cell-derived factors induce EMT.…”

“…Carcinomas are epithelial cell-derived tumors, yet they are composed of a heterogeneous mix of tumor cells that are epithelial and mesenchymal-like. Substantial evidence suggests that phenotypic plasticity allows for dedifferentiation of epithelial tumor cells resulting in expression of mesenchymal lineage markers [1–7]. This process is referred to as an epithelial to mesenchymal transition or EMT.…”