Matrix metalloproteinase-19 is a predictive marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma

AIMS: To evaluate the expression of matrix metalloproteinase-19 (MMP-19) in oropharyngeal squamous cell carcinoma along with its association with structural features of invasiveness. To investigate whether MMP-19 expression correlates with lymphatic or systemic metastasis and prognosis in patients who have received definitive radiotherapy. METHODS AND RESULTS: The histological evaluation of the invasive front was based on Bryne's malignancy grading system. We correlated the immunohistochemical expression pattern with morphological parameters which characterize tumor invasiveness such as keratinization, nuclear polymorphism, invasion pattern, and the host inflammatory response. Local immunoreactivity for MMP-19 was positively correlated with tumor invasiveness as reflected in its structural characteristics and the degree of nuclear polymorphism, and negatively correlated with the inflammatory response of the host. No correlation existed between MMP-19 expression and clinicopathological features (TNM stage, grade of differentiation) or a patient''s outcome and prognosis. CONCLUSIONS: This latter finding probably reflects the unique change for MMPs from high immunoreactivity within healthy tissue areas and non-invasive tumor parts, through absence in the least invasive neoplastic regions, to strong re-expression at a highly invasive front of the same tumor. Our findings indicate that MMP-19 can be used as a marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.

In vitro expression of the first capsule gene of Streptococcus pneumoniae, cpsA, is associated with serotype-specific colonization prevalence and invasiveness

The polysaccharide capsule protects Streptococcus pneumoniae from phagocytosis during invasive infection, but inhibits adherence. Serotypes vary in their tendency to colonize the nasopharynx or cause invasive infection, and differences in capsule expression may play a role. Expression of the first gene of the capsule operon, cpsA, during in vitro growth of 43 clinical isolates representing 14 common pneumococcal serotypes was compared using quantitative RT-PCR. Serotypes associated with invasive infection (1, 4, 5, 7F, 8 and 14) expressed an average of twofold (P=0.0003) more cpsA than serotypes associated with nasopharyngeal colonization (6A, 6B, 9V, 15, 18C, 19F, 23F and 33). There was no difference in cpsA expression in response to growth under environmental oxygen or anaerobic conditions between the invasive and colonizing transparent strains tested: oxygen concentration did not affect cpsA expression in either the invasive or the colonizing transparent strains. Expression of cpsA at OD(600) 0.6 tended to be greater in strains with a longer lag phase during in vitro growth (P=0.07). Therefore, cpsA expression under ambient oxygen concentrations correlates with serotype-specific invasiveness and is inversely associated with the prevalence of serotype-specific carriage.

Phylogenetically independent associations between autonomous self-fertilization and plant invasiveness

Many plant species have been introduced from their native ranges to new continents, but few have become naturalized or, ultimately, invasive. It has been predicted that species that do not require the presence of compatible mates and the services of pollinators for reproduction will be favored in establishment after long-distance dispersal. We tested whether this hypothesis, generally referred to as Baker's law, holds for South African species of Iridaceae ( iris family) that have been introduced in other regions for horticultural purposes. Fruit and seed production of flowers from which pollinators had been experimentally excluded was assessed for 10 pairs of species from nine different genera or subgenera. Each species pair comprised one naturalized and one nonnaturalized species, all of which are used in international horticulture. On average, species of Iridaceae that have become naturalized outside their native ranges showed a higher capacity for autonomous fruit and seed production than congeneric species that have not become naturalized. This was especially true for the naturalized species that are considered to be invasive weeds. These results provide strong evidence for the role of autonomous seed production in increasing potential invasiveness in plants.

United we stand, divided we fall: a meta-analysis of experiments on clonal integration and its relationship to invasiveness

Fragmentation and vegetative regeneration from small fragments may contribute to population expansion, dispersal and establishment of new populations of introduced plants. However, no study has systematically tested whether a high capacity of vegetative regeneration is associated with a high degree of invasiveness. For small single-node fragments, the presence of internodes may increase regeneration capacity because internodes may store carbohydrates and proteins that can be used for regeneration. We conducted an experiment with 39 stoloniferous plant species to examine the regeneration capacity of small, single-node fragments with or without attached stolon internodes. We asked (1) whether the presence of stolon internodes increases regeneration from single-node fragments, (2) whether regeneration capacity differs between native and introduced species in China, and (3) whether regeneration capacity is positively associated with plant invasiveness at a regional scale (within China) and at a global scale. Most species could regenerate from single-node fragments, and the presence of internodes increased regeneration rate and subsequent growth and/or asexual reproduction. Regeneration capacity varied greatly among species, but showed no relationship to invasiveness, either in China or globally. High regeneration capacity from small fragments may contribute to performance of clonal plants in general, but it does not appear to explain differences in invasiveness among stoloniferous clonal species.

Plant invasiveness is not linked to the capacity of regeneration from small fragments: an experimental test with 39 stoloniferous species

Fragmentation and vegetative regeneration from small fragments may contribute to population expansion, dispersal and establishment of new populations of introduced plants. However, no study has systematically tested whether a high capacity of vegetative regeneration is associated with a high degree of invasiveness. For small single-node fragments, the presence of internodes may increase regeneration capacity because internodes may store carbohydrates and proteins that can be used for regeneration. We conducted an experiment with 39 stoloniferous plant species to examine the regeneration capacity of small, single-node fragments with or without attached stolon internodes. We asked (1) whether the presence of stolon internodes increases regeneration from single-node fragments, (2) whether regeneration capacity differs between native and introduced species in China, and (3) whether regeneration capacity is positively associated with plant invasiveness at a regional scale (within China) and at a global scale. Most species could regenerate from single-node fragments, and the presence of internodes increased regeneration rate and subsequent growth and/or asexual reproduction. Regeneration capacity varied greatly among species, but showed no relationship to invasiveness, either in China or globally. High regeneration capacity from small fragments may contribute to performance of clonal plants in general, but it does not appear to explain differences in invasiveness among stoloniferous clonal species

Effects of native pollinator specialization, selfcompatibility and flowering duration of European plant species on their invasiveness elsewhere

1. When entomophilous plants are introduced to a new region, they may leave behind their usual pollinators. In particular, plant species with specialized pollination may then be less likely to establish and spread (i.e. become invasive). Moreover, other reproductive characteristics such as self-compatibility and flowering duration may also affect invasion success. 2. Here, we specifically asked whether plant species' specialization towards pollinator species and families, respectively, as measured in the native range, self-compatibility, flowering duration and their interactions are related to the degree of invasion (i.e. a measure of regional abundance) in non-native regions. 3. We used plant–pollinator interaction data from 119 German grassland sites to calculate unbiased indices of plant specialization towards pollinator species and families for 118 European plant species. We related these specialization indices, flowering duration, self-compatibility and their interactions to the degree of invasion of each species in seven large countries on four non-Eurasian continents. 4. In all models, plant species with long flowering durations had the highest degree of invasion. The best model included the specialization index based on pollinator species instead of the one based on pollinator families. Specialization towards pollinator species had a marginally significant positive effect on the degree of invasion in non-native regions for self-compatible, but not for self-incompatible species. 5. Synthesis. We showed that long flowering duration is related to the degree of invasion in other parts of the world, and a trend that pollinator generalization in the native range may interact with self-compatibility in determining the degree of invasion. Therefore, we conclude that such reproductive characteristics should be considered in risk assessment and management of introduced plant species.

Little evidence for release from herbivores as a driver of plant invasiveness from a multi-species herbivore-removal experiment

Enemy release is frequently posed as a main driver of invasiveness of alien species. However, an experimental multi-species test examining performance and herbivory of invasive alien, non-invasive alien and native plant species in the presence and absence of natural enemies is lacking. In a common garden experiment in Switzerland, we manipulated exposure of seven alien invasive, eight alien non-invasive and fourteen native species from six taxonomic groups to natural enemies (invertebrate herbivores), by applying a pesticide treatment under two different nutrient levels. We assessed biomass production, herbivore damage and the major herbivore taxa on plants. Across all species, plants gained significantly greater biomass under pesticide treatment. However, invasive, non-invasive and native species did not differ in their biomass response to pesticide treatment at either nutrient level. The proportion of leaves damaged on invasive species was significantly lower compared to native species, but not when compared to non-invasive species. However, the difference was lost when plant size was accounted for. There were no differences between invasive, non-invasive and native species in herbivore abundance. Our study offers little support for invertebrate herbivore release as a driver of plant invasiveness, but suggests that future enemy release studies should account for differences in plant size among species.

Profiling invasiveness in head and neck cancer: recent contributions of genomic and transcriptomic approaches.

High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

Hybridization as a stimulus for the evolution of invasiveness in plants?

Invasive species are of great interest to evolutionary biologists and ecologists because they represent historical examples of dramatic evolutionary and ecological change. Likewise, they are increasingly important economically and environmentally as pests. Obtaining generalizations about the tiny fraction of immigrant taxa that become successful invaders has been frustrated by two enigmatic phenomena. Many of those species that become successful only do so (i) after an unusually long lag time after initial arrival, and/or (ii) after multiple introductions. We propose an evolutionary mechanism that may account for these observations. Hybridization between species or between disparate source populations may serve as a stimulus for the evolution of invasiveness. We present and review a remarkable number of cases in which hybridization preceded the emergence of successful invasive populations. Progeny with a history of hybridization may enjoy one or more potential genetic benefits relative to their progenitors. The observed lag times and multiple introductions that seem a prerequisite for certain species to evolve invasiveness may be a correlate of the time necessary for previously isolated populations to come into contact and for hybridization to occur. Our examples demonstrate that invasiveness can evolve. Our model does not represent the only evolutionary pathway to invasiveness, but is clearly an underappreciated mechanism worthy of more consideration in explaining the evolution of invasiveness in plants.

Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site.

The mechanism(s) that regulates invasion of trophoblasts through the uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.

Insufficient Evidence of Jatropha curcas L. Invasiveness: Experimental Observations in Burkina Faso, West Africa

Biofuel plants such as Jatropha curcas L. have potential to support the livelihoods of rural communities and contribute to sustainable rural development in Africa, if risks and uncertainties are minimized. Yet, recent papers have warned of the risk of biological invasions in such tropical regions as a consequence of the introduction of exotic biofuel crops. We investigated the seed dispersal risk and invasiveness potential of both J. curcas monoculture plantations and live fences into adjacent cultivated and uncultivated land use systems in Sissili province, Burkina Faso. Invasiveness potential was assessed through (i) detecting evidence of natural regeneration in perimeters around J. curcas plantations and live fences, (ii) assessing seed dispersal mechanisms, and (iii) assessing seedling establishment potential through in situ direct seed sowing. Spontaneous regeneration around the plantation perimeters of the three sites was very low. Individual seedling density around J. curcas live fences was less than 0.01 m⁻² in all sites. Seventy percent of the seedlings were found close to the live fence and most of them derived from the same year (96 %), which indicates low seed-bank longevity and seedling survival. J. curcas can be dispersed by small mammals and arthropods, particularly rodents and ants. In some sites, such as in Onliassan, high secondary seed dispersal by animals (up to 98 %) was recorded. There were highly significant differences in germination rates between seeds at the soil surface (11 %) and those buried artificially at 1–2-cm depth (64 %). In conclusion, we failed to find convincing evidence of the spreading of J. curcas or any significant impact on the surrounding environment.

Influence of Soil Biogeochemical Properties on the Invasiveness of Old World Climbing Fern (Lygodium microphyllum)

The state of Florida has one of the most severe exotic species invasion problems in the United States, but little is known about their influence on soil biogeochemistry. My dissertation research includes a cross-continental field study in Australia, Florida, and greenhouse and growth chamber experiments, focused on the soil-plant interactions of one of the most problematic weeds introduced in south Florida, Lygodium microphyllum (Old World climbing fern). Analysis of field samples from the ferns introduced and their native range indicate that L microphyllum is highly dependent on arbuscular mycorrhizal fungi (AMF) for phosphorus uptake and biomass accumulation. Relationship with AMF is stronger in relatively dry conditions, which are commonly found in some Florida sites, compared to more common wet sites where the fern is found in its native Australia. In the field, L. microphyllum is found to thrive in a wide range of soil pH, texture, and nutrient conditions, with strongly acidic soils in Australia and slightly acidic soils in Florida. Soils with pH 5.5 - 6.5 provide the most optimal growth conditions for L. microphyllum, and the growth declines significantly at soil pH 8.0, indicating that further reduction could happen in more alkaline soils. Comparison of invaded and uninvaded soil characteristics demonstrates that L. microphyllum can change the belowground soil environment, with more conspicuous impact on nutrient-poor sandy soils, to its own benefit by enhancing the soil nutrient status. Additionally, the nitrogen concentration in the leaves, which has a significant influence in the relative growth rate and photosynthesis, was significantly higher in Florida plants compared to Australian plants. Given that L. microphyllum allocates up to 40% of the total biomass to rhizomes, which aid in rapid regeneration after burning, cutting or chemical spray, hence management techniques targeting the rhizomes look promising. Over all, my results reveal for the first time that soil pH, texture, and AMF are major factors facilitating the invasive success of L. mcirophyllum. Finally, herbicide treatments targeting rhizomes will most likely become the widely used technique to control invasiveness of L. microphyllum in the future. However, a complete understanding of the soil ecosystem is necessary before adding any chemicals to the soil to achieve a successful long-term invasive species management strategy.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Increasing the Information available to Coroners : the effect on autopsy decision making

This paper details research completed in 2007 which investigated autopsy decision making in a death investigation. The data was gathered during the first year of operation of a new Coroners Act in Queensland, Australia, which changed the process of death investigation in three ways which are important to this paper. First, it required a greater amount of information to be gathered at the scene by police, and this included a thorough investigation of the circumstances of the death, including statements from witnesses, friends and family, as well as evidence gathering at the scene. Second, it required Coroners, for the first time, to determine the level of invasiveness of the autopsy required to complete the death investigation. Third, it enabled the communication of a genuine family concern, to be communicated to the Coroner. The outcome of such information was threefold. First, a greater amount of information offered to the Coroner led to a decrease in the number of full internal autopsies ordered, but an increase in the number of partial internal autopsies ordered. Second, this shift in autopsy decision making by Coroners saw certain factors given greater importance than others in decisions to order full internal or external only autopsies. Third, a raised family concern had a significant impact on autopsy decision making and tended to decrease the invasiveness of the autopsy ordered by Coroners.