Models for Studying Cellular Invasion of Basement Membranes

SUMMARYChromatin remodeling complexes, such as the SWItching defective/Sucrose Non-Fermenting (SWI/SNF) ATP-dependent chromatin remodeling complex, coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in subunits of chromatin regulating factors are associated with a variety of diseases and cancer metastasis co-opts cellular invasion found in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin and chromatin regulating factors (CRFs) that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0/G1 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and RNA interference (RNAi), we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Finally, we implicate the SWI/SNF BAF assembly in the regulation of the cell cycle, whereas our data suggests that the SWI/SNF PBAF assembly promotes AC attachment to the basement membrane (BM) and promotes the activation of the invasive machinery. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into the contributions of SWI/SNF assembly and subunit-specific disruptions to tumorigenesis and cancer metastasis.SUMMARY STATEMENTCellular invasion through basement membranes by the C. elegans anchor cell requires both BAF- and PBAF SWI/SNF complexes to arrest the cell cycle and promote the expression of pro-invasive genes.

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Physical Properties of Isolated Perfused Renal Tubular Basement Membranes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100065997 ◽

1971 ◽

Vol 29 ◽

pp. 390-391

Author(s):

Jared Grantham ◽

Larry Welling

Keyword(s):

Basement Membrane ◽

Basement Membranes ◽

Transport Mechanisms ◽

Permeability Characteristics ◽

Peritubular Capillaries ◽

Strategic Location ◽

Tubular Lumen ◽

Glomerular Filtrate ◽

Urine Formation ◽

Renal Tubular

In the course of urine formation in mammalian kidneys over 90% of the glomerular filtrate moves from the tubular lumen into the peritubular capillaries by both active and passive transport mechanisms. In all of the morphologically distinct segments of the renal tubule, e.g. proximal tubule, loop of Henle and distal nephron, the tubular absorbate passes through a basement membrane which rests against the basilar surface of the epithelial cells. The basement membrane is in a strategic location to affect the geometry of the tubules and to influence the movement of tubular absorbate into the renal interstitium. In the present studies we have determined directly some of the mechanical and permeability characteristics of tubular basement membranes.

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A web-like network of type vi collagen in human skin is revealed by immuno-electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100103978 ◽

1988 ◽

Vol 46 ◽

pp. 382-383

Author(s):

Douglas R. Keene ◽

Robert W. Glanville ◽

Eva Engvall

Keyword(s):

Electron Microscopy ◽

Monoclonal Antibody ◽

Human Skin ◽

Basement Membranes ◽

Primary Antibody ◽

Fat Cells ◽

Secondary Antibody ◽

Type Vi Collagen ◽

Dermal Matrix ◽

Immuno Electron Microscopy

A mouse monoclonal antibody (5C6) prepared against human type VI collagen (1) has been used in this study to immunolocalize type VI collagen in human skin. The enbloc method used involves exposing whole tissue pieces to primary antibody and 5 nm gold conjugated secondary antibody before fixation, and has been described in detail elsewhere (2).Biopsies were taken from individuals ranging in age from neonate to 65 years old. By immuno-electron microscopy, type VI collagen is found to be distributed as a fine branching network closely associated with (but not attached to) banded collagen fibrils containing types I and III collagen (Fig. 1). It appears to enwrap fibers, to weave between individual fibrils within a fiber, and to span the distance separating fibers, creating a “web-like network” which entraps fibers within deep papillary and reticular dermal layers (Fig. 2). Relative to that in the dermal matrix, the concentration of type VI collagen is higher around endothelial basement membranes limiting the outer boundaries of nerves, capillaries, and fat cells (Fig. 3).

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Localization of cell-surface and basement-membrane heparan-sulfate proteoglycans using the malaria circumsporozoite protein

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100169201 ◽

1994 ◽

Vol 52 ◽

pp. 294-295

Author(s):

U. Frevert ◽

S. Sinnis ◽

C. Cerami ◽

V. Nussenzweig

Keyword(s):

Heparan Sulfate ◽

Protein A ◽

Kidney Tissue ◽

Plasmodium Species ◽

Its Region ◽

Basement Membranes ◽

Heparan Sulfate Proteoglycans ◽

Infected Mosquito ◽

Complement Components ◽

Region Ii

Malaria sporozoites, which invade hepatocytes within minutes after transmission by an infected mosquito, are covered with the circumsporozoite (CS) protein, which in all Plasmodium species contains the conserved region II-plus. This region is also found as a cell-adhesive motif in a variety of host proteins like thrombospondin, properdin and the terminal complement components.The CS protein with its region II-plus specifically binds to heparan sulfate proteoglycans (HSPG) on the basolateral surface of hepatocytes in the space of Disse (FIG. 1), to certain basolateral cell membranes and basement membranes of the kidney (FIG. 2) as well as to heparin in the granules of connective tissue mast cells. The distribution of the HSPG receptors for the CS protein was examined by incubation of Lowicryl K4M or LR White sections of liver and kidney tissue with the recombinant CS ligand, whose binding sites were detected with a monoclonal anti-CS antibody and protein A gold.

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ZUR SUBMIKROSKOPISCHEN STRUKTUR DER RATTENSCHILDDRÜSE ELEKTRONENMIKROSKOPISCHE UNTERSUCHUNGEN AN DER BASIS DES SCHILDDRÜSENFOLLIKELS

Acta Endocrinologica ◽

10.1530/acta.0.xxxv0334 ◽

1960 ◽

Vol XXXV (III) ◽

pp. 334-350 ◽

Cited By ~ 10

Author(s):

U. Waller

Keyword(s):

Endothelial Cells ◽

Basement Membranes ◽

The Other ◽

Small Vesicle ◽

Thyroid Follicle ◽

Basal Secretion ◽

Structural Principle ◽

Thyroid Epithelial Cell ◽

Endocrine Organs ◽

Subendothelial Space

ABSTRACT This is a description of ultramicroscopic structures at the base of the thyroid follicle. The structural principle of the subendothelial or interfollicular space, namely basement membranes closely following both the endothelial cells of the capillaries and the epithelial cells of the thyroid, corresponds to that described by other authors in the other endocrine organs. Especially shown are small vesicle like decreases of intensity in the subendothelial space, causing bulges in both the subepithelial basement membrane and the membrane covering the endothelial cell pores thereby forming pseudopores. This membrane is in several parts a double one. The possible role played by the above mentioned structures in the basal secretion of the thyroid epithelial cell is discussed.

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