Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma.

Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front.

miRNA control of apoptotic programs: focus on ovarian cancer.

miRNAs are a class of small non-coding RNAs that regulate the stability or translational efficiency of targeted mRNAs. miRNAs are involved in many cellular processes, such as differentiation, proliferation and apoptosis, which are altered in cancer through miRNA expression dysregulation. In this article we will discuss recent findings implicating miRNAs in apoptotic program regulation using ovarian carcinoma as an example. Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed with advanced disease that is conventionally managed with surgical resection followed by platinum-based chemotherapy. Killing of cancer cells by chemotherapeutic agents or by triggering cell-surface death receptors relies on activation of apoptotic programs executed through receptor-mediated extrinsic pathways and mitochondrial-dependent intrinsic pathways. Despite an initial good response to chemotherapy, ovarian cancer patients typically experience disease relapse within 2 years of the initial treatment developing resistance even to structurally different drugs. Thus, also in this pathology, tumor cells are able to evade apoptosis using multiple mechanisms, several of which are dependent on miRNA gene regulation.

Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.

AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment. The transcript profile of approximately 24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation-associated genes involved in pathways such as "leukocyte transendothelial migration", "cell adhesion" and "tight junctions" were differentially expressed. Moreover, gene expression levels differed significantly in urethane-treated mice; in AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice.