Tumor cell invasion of von Hippel Lindau renal cell carcinoma cells is mediated by membrane type-1 matrix metalloproteinase

BACKGROUND: Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC arising from mutations in the von Hippel Lindau (VHL) tumor suppressor. Successful RCC tumor suppression by VHL requires the negative regulation of hypoxia inducible factor alpha (HIF alpha) protein and its downstream targets. Thus, identification of HIF target genes responsible for RCC tumor progression will aid in the development of therapies for this disease. We previously identified membrane type-1 matrix metalloproteinase (MT1-MMP) as a transcriptional target of HIF-2alpha in RCC cells null for VHL and showed that MT1-MMP is overexpressed in these cells. MT1-MMP is a key regulator of tumor progression through its functions as a matrix-degrading enzyme, as well as its ability to cleave factors, such as adhesion molecules and other MMPs. The aim of this study was to investigate the contribution of MT1-MMP to the invasive potential of RCC cells using in vitro type I collagen degradation and invasion assays. RESULTS: We evaluated RCC cells wild-type (WT8) and null (pRc-9) for VHL for invasive characteristics and showed that the pRc-9 cells demonstrated a greater propensity for both invasion and degradation of a type I collagen matrix. Furthermore, overexpression of either HIF-2alpha or MT1-MMP in the poorly invasive cell line, WT8, promoted collagen degradation and invasion of these cells. Finally, using RNAi, we show that inhibition of MT1-MMP suppresses tumor cell invasion of RCC cells. CONCLUSION: Our results suggest that MT1-MMP is a major mediator of tumor cell invasiveness and type I collagen degradation by VHL RCC cells that express either MT1-MMP or HIF-2alpha. As such, MT1-MMP may represent a novel target for anti-invasion therapy for this disease

Editorial: state of the art body composition profiling: advances in imaging modalities and patient outcomes

In the last years, body composition (BC) analysis has emerged as a ground-breaking tool that can provide helpful data about nutritional status, in addition to more conventional indicators, as albumin value and body mass index. Recent data disclosed that distinct patterns of BC are associated with different outcomes, in particular in oncologic patients. Hence, we proposed this research topic, on one side, to expand knowledge about the imaging techniques to evaluate BC assessment, ranging from the most conventional ones to the most advanced (including artificial intelligence-aided techniques); on the other, to assess the effects of BC on different outcome indicators, as post-operative or chemotherapy-related complications and survival. In our research topic, we published eight papers: 3 focused on liver diseases, 1 on pancreatic cancer, 1 on ovarian cancer, 1 on lung cancer, 1 on breast cancer and 1 on radiotherapy, thus highlighting the wide variety of fields in which the clinical role of BC is under evaluation

Interleukin-1β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion through the Activation of CCAAT Enhancer Binding Protein β

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate with advanced disease. We hypothesized that IL-1b in the tumor microenvironment promotes the development of aggressive RCC tumors by directing affecting tumor epithelial cells. To address this, we investigated the role of IL-1b in mediating RCC tumor cell invasion as a measure of tumor progression. We report that IL-1b induced tumor cell invasion of RCC cells through a process that was dependent on the activity of matrix metalloproteinases (MMPs) and was independent of migration rate. Specifically, IL-1b induced the expression of MMP-1, MMP-3, MMP-10, and MT1-MMP in a mechanism dependent on IL-1b activation of the transcription factor CCAAT enhancer binding protein b (CEBP b). Consistent with its role in MMP gene expression, CEBP b knockdown significantly reduced invasion, but not migration, of RCC tumor cells. These results identify the IL-1b /CEBP b/MMP pathway as a putative target in the design of anti-metastatic therapies for the treatment of advanced RCC

Novel platinum agents and mesenchymal stromal cells for thoracic malignancies : state of the art and future perspectives

Introduction: Non-small cell lung cancer and malignant pleural mesothelioma represent two of the most intriguing and scrutinized thoracic malignancies, presenting interesting perspectives of experimental development and clinical applications. Areas covered: In advanced non-small cell lung cancer, molecular targeted therapy is the standard firstline treatment for patients with identified driver mutations; on the other hand, chemotherapy is the standard treatment for patients without EGFR mutations or ALK rearrangement or those with unknown mutation status. Once considered an ineffective therapy in pulmonary neoplasms, immunotherapy has been now established as one of the most promising therapeutic options. Mesenchymal stromal cells are able to migrate specifically toward solid neoplasms and their metastatic localizations when injected intravenously. This peculiar cancer tropism has opened up an emerging field to use them as vectors to deliver antineoplastic drugs for targeted therapies. Expert opinion: Molecular targeted therapy and immunotherapy are the new alternatives to standard chemotherapy. Mesenchymal stromal cells are a new promising tool in oncology and\u2014although not yet utilized in the clinical practice, we think they will represent another main tool for cancer therapy and will probably play a leading role in the field of nanovectors and molecular medicine

Self-estimation of Body Fat is More Accurate in College-age Males Compared to Females

Objective: To determine the effect of gender on the ability to accurately estimate one’s own body fat percentage. Participants: Fifty-five college-age males and 99 college-age females Methods: Participants estimated their own body fat percent before having their body composition measured using a BOD POD. Participants also completed a modified Social Physique Anxiety Scale (SPAS). Results: Estimated body fat was significantly lower compared to measured body fat percent in females (26.8±5.6% vs. 30.2±7.0%, p\u3c0.001) but not in males (16.8±6.8% vs. 18.1±8.3%, p=0.09). The mean difference between estimated and measured body fat was significantly higher for females compared to males (p\u3c0.001). There was a moderate, significant correlation found between measured body fat percent and SPAS score for males (r=0.331, p=0.014) and females (r=.427, p\u3c0.001). Conclusions: Males estimated their body fat percent more accurately than females. Despite these findings, 62% of males and 76% of females underestimated their body fat

Fertility preservation in ovarian tumours

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%–14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A–B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life. Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility. We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers