Driving role of head and neck cancer cell secretome on the invasion of stromal fibroblasts: Mechanistic insights by phosphoproteomics.

Background: Cancer-associated fibroblasts (CAFs) are major players in tumor-stroma communication, and participate in several cancer hallmarks to drive tumor progression and metastatic dissemination. This study investigates the driving effects of tumor-secreted factors on CAF biology, with the ultimate goal of identifying effective therapeutic targets/strategies for head and neck squamous cell carcinomas (HNSCC).

Methods: Functionally, conditioned media (CM) from different HNSCC-derived cell lines and normal keratinocytes (Kc) were tested on the growth and invasion of populations of primary CAFs and normal fibroblasts (NFs) using 3D invasion assays in collagen matrices.

Prognostic Relevance of CD4, CD8 and FOXP3 TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers.

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4, CD8 and FOXP3 TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed.

Stathmin as a surrogate marker of phosphatidylinositol-3-kinase pathway activity: Towards precision medicine in HPV-negative head & neck squamous cell carcinoma.

In order to assess Stathmin as an immunohistochemical (IHC) indicator of phosphatidylinositol 3-kinase (PI3K) pathway activity in HPV-negative head & neck squamous cell carcinoma (HNSCC), we compared Stathmin IHC to expression of other pathway components. We also evaluated the relationship between Stathmin IHC and the mutational status of four key pathway genes. Finally, we ascertained whether Stathmin IHC correlates with tumor grade or primary site.

Expression of E-cadherin and β-catenin in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas.

Introduction And Objectives: Dysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development. The aim of this paper is to investigate the prognostic significance of E-cadherin and β-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas.

Material And Methods: Tumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005.

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications.

Stemness in sarcomas is coordinated by the expression of pluripotency factors, like SOX2, in cancer stem cells (CSC). The role of SOX2 in tumor initiation and progression has been well characterized in osteosarcoma. However, the pro-tumorigenic features of SOX2 have been scarcely investigated in other sarcoma subtypes.

Deciphering the Molecular Basis of Melatonin Protective Effects on Breast Cells Treated with Doxorubicin: TWIST1 a Transcription Factor Involved in EMT and Metastasis, a Novel Target of Melatonin.

Melatonin mitigates cancer initiation, progression and metastasis through inhibition of both the synthesis of estrogens and the transcriptional activity of the estradiol-ER (Estrogen receptor) complex in the estrogen-dependent breast cancer cell line MCF-7. Moreover, melatonin improves the sensitivity of MCF-7 to chemotherapeutic agents and protects against their side effects. It has been described that melatonin potentiates the anti-proliferative effects of doxorubicin; however, the molecular changes involving gene expression and the activation/inhibition of intracellular signaling pathways remain largely unknown.

YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib.

The characterization of new genetic alterations is essential to assign effective personalized therapies in non-small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of , a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer.

Correlation of focal adhesion kinase expression with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

Background: Focal adhesion kinase (FAK) and cortactin overexpression is frequently detected in a variety of cancers, and has been associated with poor clinical outcome. However, there are no data in cutaneous squamous cell carcinoma (cSCC).

Objective: To investigate the relationship of FAK and cortactin expression with the clinicopathologic features and the impact on the prognosis of cSCC patients.

Mutational profiling can identify laryngeal dysplasia at risk of progression to invasive carcinoma.

Early diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of dysplasia could greatly improve the outcome of affected patients. For the first time we compared the mutational landscape of non-progressing dysplasia (NPD; n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC biopsies; a total of 90 samples. Using targeted next-generation sequencing identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, FBXW7), and mutations were validated by Sanger sequencing and/or qPCR.

Analysis of Invasive Activity of CAF Spheroids into Three Dimensional (3D) Collagen Matrices.

Tumor growth and progression is the result of a complex process controlled not only by malignant cancer cells but also by the surrounding tumor microenvironment (TME). Cancer associated fibroblasts (CAFs), the most abundant cellular component of TME, play an active role in tumor invasion and metastasis by promoting cancer cell invasion through cell-cell interactions and secretion of pro-invasive factors such as extracellular matrix (ECM)-degrading proteases. Due to their tumor-promoting activities, there is an emerging interest in investigating CAFs biology and its potential as drug targets for cancer therapies.

FUS-CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK-Dependent Pathway.

Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many types of tumors. In myxoid and round cell liposarcoma (MRCLS), an adipocytic tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have been found as one of the most activated kinases. Here we used a cell-of-origin model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays) and in vivo (chicken chorioallantoic membrane model) approaches.

Tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck.

Background: Binding of tumor-expressed programmed cell death ligand 1 (PD-L1) to the programmed cell death 1 (PD-1) surface receptor blocks T-cell activation thereby leading to immune evasion. Tumor PD-L1 expression has been associated with poor outcome in a wide variety of cancers; however, data in cutaneous squamous cell carcinoma (cSCC) are scarce and conflicting.

Objective: To investigate the relationship of tumor PD-L1 expression with the clinicopathologic features and prognosis of cSCC.

Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models.

Trabectedin has been approved for second-line treatment of soft tissue sarcomas. However, its efficacy to target sarcoma initiating cells has not been addressed yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and undifferentiated pleomorphic sarcoma (UPS) developed from transformed human mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in the cell type responsible for initiating sarcomagenesis and their derived cancer stem cells (CSC) subpopulations.

Impact of PI3K/AKT/mTOR pathway activation on the prognosis of patients with head and neck squamous cell carcinomas.

The PI3K/AKT/mTOR signaling pathway has emerged as one of the most frequently deregulated in head and neck squamous cell carcinomas (HNSCC). Numerous alterations of various upstream and downstream components have been described; however, their prognostic significance and impact on HNSCC patient survival remains to be established. This was addressed using an unbiased cohort of 93 consecutive and homogeneous surgically treated HNSCC patients and results confirmed in 432 HNSCC patients.

Clinical significance of Anoctamin-1 gene at 11q13 in the development and progression of head and neck squamous cell carcinomas.

This study investigates the clinical significance of Anoctamin-1 gene mapping at 11q13 amplicon in both the development and progression of head and neck squamous cell carcinomas (HNSCC). ANO1 protein expression was evaluated by immunohistochemistry in a cohort of 372 surgically treated HNSCC patients and also in 35 laryngeal precancerous lesions. ANO1 gene amplification was determined by real-time PCR in all the laryngeal premalignancies and 60 of the HNSCCs, and molecular data correlated with clinical outcome.

Expression of podoplanin in the invasion front of oral squamous cell carcinoma is not prognostic for survival.

Podoplanin is involved in actin remodeling of the cytoskeleton of tumor cells and may promote tumor cell invasion by increasing cell motility and formation of filopodia-like membrane protrusions. Podoplanin is expressed in a variety of tumors, but its role in head and neck cancer, particularly in oral squamous cell carcinoma, remains unclear. We studied podoplanin expression by immunohistochemistry in 92 oral squamous cell carcinomas (OSCC) using a monoclonal antibody against an epitope of podoplanin (D2-40).

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.

NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation.

Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas.

Metastasis remains a major cause of mortality in head and neck squamous cell carcinoma (HNSCC). Current clinicopathological features have shown limited predictability for the risk of distant metastasis in individual patients, and therefore more accurate and reliable markers are needed. The aim of this study was to investigate the ability of various molecular markers present in primary tumors to predict the risk of developing distant metastasis.

Podoplanin expression in oral leukoplakia: tumorigenic role.

Objectives: Recent studies have identified podoplanin, a mucin-type transmembrane glycoprotein, as a biomarker for oral cancer risk in patients with oral leukoplakia (OPL). The aim of this study was to investigate the potential association between podoplanin and the risk of malignant transformation of OPL with epithelial dysplasia.

Materials And Methods: In this retrospective study, podoplanin immunoexpression was analyzed in 58 patients with oral leukoplakia that showed epithelial dysplasia.

Frequent aberrant expression of the human ether à go-go (hEAG1) potassium channel in head and neck cancer: pathobiological mechanisms and clinical implications.

Compelling evidence indicates that the human ether-à-go-go voltage-gated potassium channels (hEAG1) may represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investigate the expression of hEAG1 potassium channel subunit in both primary tumors and HNSCC-derived cell lines to ascertain its clinical and biological role in tumor progression. Our findings demonstrate that hEAG1 is frequently aberrantly expressed in a high percentage of primary tumors (83 %, 45/54 cases) and HNSCC-derived cell lines (83 %, 10/12 cell lines).

Cortactin and focal adhesion kinase as predictors of cancer risk in patients with premalignant oral epithelial lesions.

There is a need for novel and accurate biomarkers based on genetic abnormalities capable of predicting the risk of malignant transformation of epithelial lesions of the oral cavity. Therefore, we investigate the role of cortactin and focal adhesion kinase (FAK) protein expression in oral dysplasias and their potential utility as cancer risk markers. Cortactin and FAK expression were immunohistochemically evaluated in 64 patients with oral epithelial dysplasia.

Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review.

Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions.

Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy.

Novel markers are needed to accurately predict the risk of malignant transformation in laryngeal premalignancies. We therefore investigated the clinical significance of cortactin (CTTN) and focal adhesion kinase (FAK) during laryngeal tumorigenesis and their potential utility as cancer risk markers. CTTN and FAK protein expression and gene amplification were assessed in 82 patients with laryngeal dysplasia and correlated with clinicopathologic parameters and laryngeal cancer risk.

Annexin A2 localizes to the basal epithelial layer and is down-regulated in dysplasia and head and neck squamous cell carcinoma.

Annexin A2 is a highly expressed gene with important roles in cell membrane physiology and is frequently dysregulated in cancer. The objective of this study was to determine the pattern of expression and prognostic significance of annexin A2 protein in head and neck squamous cell carcinoma. We assessed both quantitative changes and qualitative distribution of annexin A2 mRNA and protein expression in normal and diseased tissues by immunohistochemistry, immunofluorescence and in situ hybridization.

Annexin A1 expression in nasopharyngeal carcinoma correlates with squamous differentiation.

Background: Alterations of annexin A1 (ANXA1) expression have been reported in various cancers. However, no data are available about the expression of this protein in nasopharyngeal carcinomas (NPCs). The objective of this study was to investigate the expression of ANXA1 in these tumors.