Abstract
Epithelial-mesenchymal transition (EMT) is important for tumor metastasis. Detection of EMT protein expression and observation of morphological changes are commonly used to identify EMT. Diffusion-weighted magnetic resonance imaging (DW-MRI) and measuring apparent diffusion coefficient (ADC) values are noninvasive techniques for characterizing tumor microenvironments. We investigated the difference in ADC values between epithelial- and mesenchymal-like subcutaneous mouse xenografted tumors using DW-MRI. Epithelial-like MM189 PB-Klf4 and BL322 PB-Klf4 cells were generated from tumor suppressive Kruppel-like factor 4 (Klf4)-expressing mesenchymal-like MM189 and BL322 cells. The ADC values of xenografted tumors from epithelial-like MM189 PB-Klf4 and BL322 PB-Klf4 were significantly lower than those from their mesenchymal-like counterparts (p < 0.05 and p < 0.01, respectively). Our results suggested that DW-MRI is a potential tool for observing mesenchymal- or epithelial-like characteristics of subcutaneous xenografted tumors.
Highlights
Excessive cell proliferation and angiogenesis are hallmarks of the initiation and early growth of primary epithelial cancers [1]
We investigated the relationship between apparent diffusion coefficient (ADC) values and epithelial-/mesenchymal-like phenotypes using mouse xenografted tumor models generated from established liver cancer cells
Epithelial- or Mesenchymal-Like Xenografted Tumors Generated from Kruppel-Like Factor 4 (Klf4) or Vector Control Expressing Mesenchymal-Like Cells
Summary
Excessive cell proliferation and angiogenesis are hallmarks of the initiation and early growth of primary epithelial cancers [1]. The subsequent acquisition of invasiveness is thought to be the onset of late-stage tumorigenesis. The activation of an epithelial-mesenchymal transition (EMT) process with an important role in invasion and metastasis has been proposed as the critical mechanism for acquisition of malignant phenotypes by epithelial cancer cells [2,3,4]. EMT is a key step during embryonic morphogenesis, heart development, chronic degenerative fibrosis, and cancer progression [5]. EMT, epithelial cancer cells lose many of their epithelial characteristics, acquire mesenchymal cell properties, show reduced intercellular adhesion, display increased motility, and promote tumor metastasis [4,6]. Low E-cadherin, high vimentin, and N-cadherin expression are traditional markers used to identify cells that have undergone EMT [7,8]
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