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J.Jpn. Surg. Soc.. 119(3): 286-292, 2018
THERAPEUTIC PERSPECTIVE ON THE TUMOR MICROENVIRONMENT IN NON-SMALL-CELL LUNG CANCER
The tumor microenvironment is composed of different types of stromal cells that represent a key component of tumor progression. We reported that transforming growth factor (TGF)-β
signaling mediates the epithelial mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) cells, and that TGF-β
-induced changes are associated with insensitivity to treatment such as chemotherapy or radiation. In order to identify new targets for the prevention of metastasis, it is important to understand the molecular mechanisms that drive the EMT. Tumor-localized fibroblasts, so-called cancer-associated fibroblasts (CAFs), can comprise more than half of the tumor mass, and active multidirectional communications take place between these co-evolving cell types within cancer tissue. We showed that interleukin-6 from CAFs enhanced the TGF-β
-induced EMT in NSCLC cells. These cytokines produced by stromal cells may contribute to the maintenance of a paracrine loop that functions as part of the communication between CAFs and NSCLC cells, resulting in increased malignant potential and the acquisition of stemness by NSCLC tumors. Decreased expression of epithelial markers and upregulation of mesenchymal markers were detected in surgically resected specimens after chemoradiotherapy compared with biopsy specimens obtained before treatment. A diffuse distribution of CAFs was correlated with EMT changes in cancer cells. Targeting CAFs as a therapeutic strategy against cancer is an intriguing concept that would benefit from further study.
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