BranchAnalysis2D/3D automates morphometry analyses of branching structures.

Background: Morphometric analyses of biological features have become increasingly common in recent years with such analyses being subject to a large degree of observer bias, variability, and time consumption. While commercial software packages exist to perform these analyses, they are expensive, require extensive user training, and are usually dependent on the observer tracing the morphology.

New Method: To address these issues, we have developed a broadly applicable, no-cost ImageJ plugin we call 'BranchAnalysis2D/3D', to perform morphometric analyses of structures with branching morphologies, such as neuronal dendritic spines, vascular morphology, and primary cilia.

Suppression of integrin α3β1 by α9β1 in the epidermis controls the paracrine resolution of wound angiogenesis.

Development of wound therapies is hindered by poor understanding of combinatorial integrin function in the epidermis. In this study, we generated mice with epidermis-specific deletion of α3β1, α9β1, or both integrins as well as keratinocyte lines expressing these integrin combinations. Consistent with proangiogenic roles for α3β1, α3-null keratinocytes showed reduced paracrine stimulation of endothelial cell migration and survival, and wounds of epidermis-specific α3 knockout mice displayed impaired angiogenesis.

Focal adhesion kinase is a phospho-regulated repressor of Rac and proliferation in human endothelial cells.

Focal adhesion kinase (FAK) is critically positioned to integrate signals from the extracellular matrix and cellular adhesion. It is essential for normal vascular development and has been implicated in a wide range of cellular functions including the regulation of cell proliferation, migration, differentiation, and survival. It is currently being actively targeted therapeutically using different approaches.

Endostatin and anastellin inhibit distinct aspects of the angiogenic process.

Background: Endostatin and anastellin, fragments of collagen type XVIII and fibronectin, respectively, belong to a family of endogenous inhibitors of angiogenesis which inhibit tumor growth and metastasis in a number of mouse models of human cancer. The mechanism of action of these inhibitors is not well understood, but they have great potential usefulness as non-toxic long-term therapy for cancer treatment.

Methods: In this study, we compare the anti-angiogenic properties of endostatin and anastellin using cell proliferation and transwell migration assays.

An immortalization-dependent switch in integrin function up-regulates MMP-9 to enhance tumor cell invasion.

Integrins, the major receptors for cell adhesion to the extracellular matrix, play important roles during tumor progression. However, it is still unclear whether genetic lesions that occur during carcinoma development can lead to altered integrin function, and how changes in integrin function contribute to subsequent carcinoma progression. Loss-of-function mutations in p53 and activating mutations in H-Ras, which immortalize and transform epithelial cells, respectively, are common causal events in squamous cell carcinoma (SCC).

Integrin alpha3beta1-dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on laminin-5.

Upon epidermal wounding, keratinocytes at the wound edge become activated, deposit newly synthesized laminin-5 into the extracellular matrix, and migrate into the wound bed. The interaction between integrin alpha3beta1 and laminin-5 is essential for establishment of a stable, leading lamellipodium and persistent keratinocyte migration. We previously showed that integrin alpha3beta1 activates the Rho family GTPase Rac1 and regulates Rac1-dependent formation of polarized, leading lamellipodia in migrating keratinocytes.

Activation of p38 has opposing effects on the proliferation and migration of endothelial cells.

Pathological conditions such as hypertension and hyperglycemia as well as abrasions following balloon angioplasty all lead to endothelial dysfunction that impacts disease morbidity. These conditions are associated with the elaboration of a variety of cytokines and increases in p38 activity in endothelial cells. However, the relationship between enhanced p38 activity and endothelial cell function remains poorly understood.

Anastellin, a fragment of the first type III repeat of fibronectin, inhibits extracellular signal-regulated kinase and causes G(1) arrest in human microvessel endothelial cells.

The formation of a microvascular endothelium plays a critical role in the growth and metastasis of established tumors. The ability of a fragment from the first type III repeat of fibronectin (III(1C)), anastellin, to suppress tumor growth and metastasis in vivo has been reported to be related to its antiangiogenic properties, however, the mechanism of action of anastellin remains unknown. Utilizing cultures of human dermal microvascular endothelial cells, we provide evidence that anastellin inhibits signaling pathways which regulate the extracellular signal-regulated (ERK) mitogen-activated protein kinase pathway and subsequent expression of cell cycle regulatory proteins.

Activated Ras induces a proangiogenic phenotype in primary endothelial cells.

Angiogenic factors alter endothelial cell phenotype to promote the formation of new blood vessels, a process critical for a number of normal and pathological conditions. Ras is required for the induction of the angiogenic phenotype in response to vascular endothelial growth factor (VEGF). However, VEGF generates many signals, several of which are not dependent upon Ras activation.