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Aims Neuropilin-1 ( NRP1) and neuropilin-2 ( NRP2) are transmembrane glycoproteins which interact with vascular endothelial growth factor ( VEGF) to prevent tumour cell apoptosis and regulate angiogenesis. However, the precise role of NRP1 and NRP2 in the adenoma-carcinoma sequence ( ACS) of colorectal cancer remains unclear, and we aimed to determine this in surgical specimens comprising the ACS. Methods and results Histological analysis demonstrated that epithelial NRP1 expression increased significantly across the ACS ( P = 0.0007), and correlated with microvessel density ( MVD; r = 0.505, P = 0.0003) and weakly with VEGF ( r = 0.251, P = 0.001). In contrast, although NRP2 epithelial expression was increased significantly in all carcinomas ( P < 0.002), there was no correlation with MVD, VEGF or NRP1. Furthermore, patients showing coexpression of NRP1 and NRP2 had a potentially worse prognosis than those expressing a single neuropilin or neither one. Although vascular expression of NRP1 increased significantly across the ACS ( P = 0.0004) and correlated with MVD ( r = 0.361, P = 0.0006), NRP2 vascular expression decreased significantly ( P = 0.0001) and showed an inverse correlation with MVD ( r=−0.506, P = 0.0001), suggesting differential roles for neuropilins in the angiogenic process during colorectal cancer development. Conclusions These data suggest that an increase in NRP1 and NRP2 epithelial/tumour expression, as well as in NRP1 vascular expression, may be associated with disease progression in colorectal cancer. [ABSTRACT FROM AUTHOR]

Summary Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRP's role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium. [ABSTRACT FROM AUTHOR]

Summary Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases. ADAMTS-1 and ADAMTS-8 have been reported to be anti-angiogenic. Here, we provide evidence that ADAMTS-4, like ADAMTS-1, is expressed by endothelial cells and binds to vascular endothelial groth factor (VEGF). Moreover, ADAMTS-4 inhibited human dermal microvascular endothelial cells (HuDMEC) VEGF-stimulated VEGF receptor (R) R2 phosphorylation, differentiation and migration, suggesting that ADAMTS-4 may be a novel anti-angiogenic molecule. [ABSTRACT FROM AUTHOR]

Staton C A, Hoh L, Baldwin A, Shaw L, Globe J, Cross S S, Reed M W & Brown N J (2011) Histopathology 59, 256-263 Angiopoietins 1 and 2 and Tie-2 receptor expression in human ductal breast disease Aims: This study aimed to identify the involvement of the angiopoietin/Tie-2 receptor system in breast cancer development, progression, metastasis and angiogenesis. Methods and results: We quantified and correlated angiopoietin-1 (Ang-1), Ang-2 and Tie-2 expression in sections of normal human breast, benign and premalignant hyperplastic tissue, pre-invasive and invasive cancer, and compared these findings with our previously published data on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the same samples. A breast cancer tissue microarray was used to evaluate the prognostic value of these factors. Histological analysis revealed a significant decrease in Ang-1 expression ( P = 0.001) and an inverse correlation with MVD ( r = −0.442, P = 0.008) and VEGF ( r = −0.510, P = 0.002) in the non-invasive lesions. In contrast Ang-2 expression increased significantly ( P = 0.0004) with increasing severity of lesion and correlated with MVD ( r = 0.570; P = 0.0002), while Tie-2 expression remained relatively unchanged. Expression of all three factors was reduced in invasive breast cancer and did not correlate with oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), lymph node status or tumour grade. Conclusions: These data suggest that a change in the angiopoietin balance in favour of Ang-2 is associated with the angiogenic switch at the onset of hyperplasia in the breast. However, angiopoietins and the Tie-2 receptor are not related to known prognostic indicators in invasive breast cancer. [ABSTRACT FROM AUTHOR]

Staton C A, Shaw L A, Valluru M, Hoh L, Koay I, Cross S S, Reed M W & Brown N J (2011) Histopathology 59, 274-282 Expression of class 3 semaphorins and their receptors in human breast neoplasia Aims: This study aimed to identify the involvement of class 3 semaphorins (Sema3) and receptors, neuropilins (Np1 and Np2) and plexins (A1-A4) in breast cancer development and angiogenesis. Methods and results: We quantified and correlated Sema3A, Sema3B, Sema3F and their known receptors and coreceptors Plexin-A1, Plexin-A3, Np1 and Np2 in sections of normal human breast, benign and pre-malignant hyperplastic tissue, pre-invasive and invasive cancer, and compared these findings with our previously published data on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the same samples. Histological analysis revealed that Sema3B was expressed more strongly and widely than Sema3A and 3F in normal breast tissue and all three semaphorins decreased with the transition from in situ to invasive cancer ( P < 0.014). Plexin-A3 decreased significantly with progression towards invasive cancer ( P < 0.045), whereas Plexin-A1 expression was only significantly reduced once invasion had occurred ( P = 0.012). Np1 and Np2 were expressed in both endothelial and epithelial/tumour cells. Np2 expression did not change, but Np1 expression significantly increased in the spectrum from hyperplasia to ductal carcinoma in situ ( P < 0.035), but decreased with invasive cancer. Conclusion: These data suggest that a decrease in class 3 semaphorin and their plexin receptors have some relationship with disease progression in ductal breast carcinoma. [ABSTRACT FROM AUTHOR]

Summary With over thirty different hormones identified as being produced in the gastrointestinal (GI) tract, the gut has been described as 'the largest endocrine organ in the body' ( Ann. Oncol., 12, 2003, S63). The classification of these hormones and the cells that produce them, the enteroendocrine cells (EECs), has provided the foundation for digestive physiology. Furthermore, alterations in the composition and function of EEC may influence digestive physiology and thereby associate with GI pathologies. Whilst there is a rapidly increasing body of data on the role and function of EEC in the upper GI tract, there is a less clear-cut understanding of the function of EEC in the lower GI. Nonetheless, their presence and diversity are indicative of a role. This review focuses on the EECs of the lower GI where new evidence also suggests a possible relationship with the development and progression of primary adenocarcinoma. [ABSTRACT FROM AUTHOR]

The study of angiogenesis has grown exponentially over the past 40 years with the recognition that angiogenesis is essential for numerous pathologies and, more recently, with the advent of successful drugs to inhibit angiogenesis in tumours. The main problem with angiogenesis research remains the choice of appropriate assays to evaluate the efficacy of potential new drugs and to identify potential targets within the angiogenic process. This selection is made more complex by the recognition that heterogeneity occurs, not only within the endothelial cells themselves, but also within the specific microenvironment to be studied. Thus, it is essential to choose the assay conditions and cell types that most closely resemble the angiogenic disease being studied. This is especially important when aiming to translate data from in vitro to in vivo and from preclinical to the clinic. Here we critically review and highlight recent advances in the principle assays in common use including those for endothelial cell proliferation, migration, differentiation and co-culture with fibroblasts and mural cells in vitro, vessel outgrowth from organ cultures and in vivo assays such as chick chorioallantoic membrane (CAM), zebrafish, sponge implantation, corneal, dorsal air sac, chamber and tumour angiogenesis models. Finally, we briefly discuss the direction likely to be taken in future studies, which include the use of increasingly sophisticated imaging analysis systems for data acquisition. [ABSTRACT FROM AUTHOR]

Angiogenesis, the development of new blood vessels from an existing vasculature, is essential in normal developmental processes and in numerous pathologies, including diabetic retinopathy, psoriasis and tumour growth and metastases. One of the problems faced by angiogenesis researchers has been the difficulty of finding suitable methods for assessing the effects of regulators of the angiogenic response. The ideal assay would be reliable, technically straightforward, easily quantifiable and, most importantly, physiologically relevant. Here, we review the advantages and limitations of the principal assays in use, including those for the proliferation, migration and differentiation of endothelial cellsin vitro, vessel outgrowth from organ cultures andin vivoassays such as sponge implantation, corneal, chamber, zebrafish, chick chorioallantoic membrane (CAM) and tumour angiogenesis models. [ABSTRACT FROM AUTHOR]