Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.     

Floating mist nets: a technique for capturing birds in flooded habitat

ABSTRACT.   Banding birds is essential for detailed demographic studies of avian populations. Mist nets are a widely used, effective method of capturing birds for banding, but are difficult to use under certain conditions. While conducting a demographic study of Southwestern Willow Flycatchers ( Empidonax traillii extimus ), rising reservoir levels flooded large tracts of flycatcher breeding habitat and made traditional mist-netting techniques impossible to use. In response, we devised a technique for capturing birds over deep water using mist nets suspended between poles kept afloat on compact buoys. In 2005, we used this technique to safely capture 17 Willow Flycatchers that could not have been captured by any other means, and over 40 additional passerines were incidentally captured with no injuries occurring. This versatile apparatus was simple to build and employ, and capture success was similar to that over dry land.     

Is the keystone role of figs maintained across a gradient of increasing human disturbance?

Fig trees provide important resources to tropical animals, but is their keystone role affected by human disturbance? In Sri Lanka, we found that more bird species were found in close association with fruiting figs in urban areas, suggesting their role is accentuated there, and justifying their planting.     

Immunohistochemical Analysis of the Mechanistic Target of Rapamycin and Hypoxia Signalling Pathways in Basal Cell Carcinoma and Trichoepithelioma

Background

Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways.

Objectives

To determine whether HIF1/mTOR signalling is involved in BCC and TE.

Methods

We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, <30%, 30–80% and >80%).

Results

Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included.

Conclusions

HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.     

Asymmetry of larval diet breadth and oviposition preference in Leptinotarsa undecimlineata

The relationship between preference and performance was studied under laboratory conditions for larvae and adult females of Leptinotarsa undecimlineata (Stål) (Coleoptera: Chrysomelidae). Leptinotarsa undecimlineata feeds exclusively on Solanum lanceolatum L. (Solanaceae) in the centre of Veracruz, Mexico. A common sympatric species, Solanum myriacanthum Dunal, is not used as host. We conducted a series of laboratory experiments to detect reasons for the exclusive use of one host plant. Leptinotarsa undecimlineata larvae were reared under laboratory conditions on both plant species, Solanum lanceolatum and S. myriacanthum . Length of larval stages, pupal weight, and percent adult eclosion were compared, and larval preference for both Solanum species was tested. Upon eclosion, adult females were exposed to each of the plants, and the effect of larval diet on adult preference was determined. Oviposition on both Solanum species was observed in no-choice tests. Larvae showed no significant preferences for either plant species. Pupal weight, however, was significantly higher on S. lanceolatum . Female beetles significantly preferred S. lanceolatum leaves, and no effect of preimaginal conditioning was found. Females reproduced in lower numbers after feeding on S. myriacanthum , oviposition initiated later, and females laid fewer eggs than females fed with S. lanceolatum . No female accepted S. myriacanthum for oviposition. Results obtained suggest that the potential host breadth of L. undecimlineata is broader in larvae than in female beetles.     

Assessing the potential of translocating vulnerable forest birds by searching for novel and enduring climatic ranges

Hawaiian forest birds are imperiled, with fewer than half the original >40 species remaining extant. Recent studies document ongoing rapid population decline and project complete climate‐based range losses for the critically endangered Kaua'i endemics ‘akeke’e (Loxops caeruleirostris) and ‘akikiki (Oreomystis bairdi) by end‐of‐century due to projected warming. Climate change facilitates the upward expansion of avian malaria into native high elevation forests where disease was historically absent. While intensified conservation efforts attempt to safeguard these species and their habitats, the magnitude of potential loss and the urgency of this situation require all conservation options to be seriously considered. One option for Kaua’i endemics is translocation to islands with higher elevation habitats. We explored the feasibility of interisland translocation by projecting baseline and future climate‐based ranges of ‘akeke’e and ‘akikiki across the Hawaiian archipelago. For islands where compatible climates for these species were projected to endure through end‐of‐century, an additional climatic niche overlap analysis compares the spatial overlap between Kaua’i endemics and current native species on prospective destination islands. Suitable climate‐based ranges exist on Maui and Hawai'i for these Kaua'i endemics that offer climatically distinct areas compared to niche distributions of destination island endemics. While we recognize that any decision to translocate birds will include assessing numerous additional social, political, and biological factors, our focus on locations of enduring and ecologically compatible climate‐based ranges represents the first step to evaluate this potential conservation option. Our approach considering baseline and future distributions of species with climatic niche overlap metrics to identify undesirable range overlap provides a method that can be utilized for other climate‐vulnerable species with disjointed compatible environments beyond their native range.     

Decellularized tissue and cell-derived extracellular matrices as scaffolds for orthopaedic tissue engineering

The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic.